Physiological Aspects of Digestion and Metabolism in Ruminants: Proceedings of the Seventh International Symposium on Ruminant Physiology

Association.

part 1

Physiology of the Digestive Tract

1

Regulation of Gut Motility by Luminal Stimuli in the Ruminant

David F. Cottrell,     Department of Preclinical Veterinary Sciences, University of Edinburgh, Edinburgh, Scotland

Peter C. Gregory,     Sparte Pharmazeutika, Abteilung P-FPG, Kalchemie AG, Hanover, Federal Republic of Germany

Publisher Summary

Luminal stimuli play an important role in the regulation of gastrointestinal motility. The volume and composition of digesta initiate motility patterns by activating neural and hormonal mechanisms. The chapter deals with the neural mechanisms involved and concentrates on experiments utilizing physiological preparations where the stimuli are within normal limits. Using this approach makes it easy to deduce the importance of the mechanisms involved in the intact animal. Luminal stimuli include distention, tactile, chemical, viscosity, and possibly thermal changes. The regulatory mechanisms by luminal stimuli are modified by factors such as fasting, inherent circadian rhythms, and the postprandial release of GI-tract and other hormones—all of which require further study and appropriate experimental procedures.

I. Innervation of the Gastrointestinal Tract

A. Motor Control

B. Sensory Mechanisms

C. Alimentary Enteroceptors

II. CNS-Mediated Responses

A. Stimuli to Buccal Cavity and Esophagus

B. Stimuli to Reticulorumen

C. Stimuli to Omasum

D. Stimuli to Abomasum

E. Stimuli to the Small Intestine

F. Stimuli to the Ileum

G. Stimuli to the Large Intestine

III. Spinal Reflex Mechanisms

IV. Peripheral Reflexes via the Prevertebral Ganglia

V. Intrinsic Reflexes via the Enteric Nervous System

A. Reticulorumen

B. Omasum

C. Abomasum and Large Intestine

D. Small Intestine

VI. Humoral Mechanisms

A. Stimuli to the Reticulorumen

B. Stimuli to the Abomasum

C. Stimuli to the Duodenum

VII. Conclusions

References

Luminal stimuli play an important role in the regulation of gastrointestinal motility. The volume and composition of digesta can interrupt or initiate motility patterns by activating neural and hormonal mechanisms. This review deals principally with the neural mechanisms involved, as far as they are known, and concentrates on experiments utilizing physiological preparations where the stimuli are apparently within normal limits. By using this approach, we may be able to deduce the importance of the mechanisms involved in the intact animal. Luminal stimuli include distention, tactile, chemical, viscosity, and possibly thermal changes.

I. Innervation of the Gastrointestinal Tract

A. Motor Control

The smooth muscle of the alimentary canal is richly innervated by autonomic and visceral afferent fibers. Neural control of motility is organized at various (interconnected) levels; central nervous system (CNS) control via parasympathetic and sympathetic nerves; intermediate reflexes via prevertebral and paravertebral ganglia; and local reflexes via the enteric nervous system (Gonella et al. 1987; Wood 1987). Both autonomic and afferent fibers occupy the same peripheral nerves. The parasympathetic vagal supply extends from the esophagus to the proximal colon and comprises, in those animals studied which do not include the ruminant, afferent and efferent fibers in a ratio of greater than 9 : 1. The distal colon is supplied by the pelvic nerves. The parasympathetic innervation of muscle is indirect via the enteric neurons. There is approximately one vagal efferent fiber to 10,000 enteric neurons; each vagal preganglionic axon innervates a relatively large cluster of enteric ganglia, and thus appears to behave as a command neurone. In the small intestine there may be local integrative circuits of enteric neurons, preprogrammed for control of distinct motility patterns, which receive commands from the CNS via autonomic fibers (Wood 1987). The vagus of animals with simple stomachs contains two functionally distinct pathways: one to excitatory cholinergic neurons and another to inhibitory nonadrenergic noncholinergic neurons (Gonella et al. 1987). We are recently beginning to obtain evidence for a similar specificity in the ruminant (Reid et al. 1988a; Reid et al. 1988b).

Sympathetic preganglionic fibers leave the spinal cord through the ventral roots, and many synapse in prevertebral ganglia with noradrenergic postganglionic neurons, which travel in mesenteric and colonic nerves. Most sympathetic fibers travel to the enteric nervous system where they cause presynaptic (α2) inhibition of acetylcholine release. Some sympathetic fibers directly innervate the muscle (by α and β receptors) especially at sphincters, and others connect with 5HT neurons (Gonella et al. 1987; Wood 1987). Afferent axons travel along the same pathways as sympathetic fibers where they outnumber efferent fibers by 3 : 1 in the cat. Afferent fibers generally enter the spinal cord via the dorsal roots, although in the cat (Clifton et al. 1976), sacral nerves may enter the ventral roots. The enteric nervous system comprises a number of interconnected ganglionated plexuses, two of which are the submucous (Meissner’s) plexus lying in the submucosa and the myenteric (Auerbach’s) plexus lying at the boundary of the longitudinal and circular muscular layers and supplying the major innervation of these muscles (Wood 1987). The details of intrinsic and ganglionic involvement in sensory and reflex pathways have largely been ignored in the ruminant.

B. Sensory Mechanisms

A principal mechanism to detect alterations in the environment of the alimentary lumen is the visceral afferent system. GI enteroceptor excitation reflexly activates postprandial motor activity via extrinsic, intrinsic, and intermediate (ganglionic) pathways, as well as playing a role in the regulation of food intake. It is not yet known whether the same receptor mechanisms activate enteric reflexes and also project toward the CNS. As yet there is little direct evidence for a structural correlate of most alimentary enteroceptors. There is also little evidence to support the concept of selective sensitivity of alimentary sensory receptors in the ruminant as is found in animals with simple stomachs (Leek 1972a; Leek 1977). Afferent endings are mostly unmyelinated, and their sensitivity may be altered by the environment in which they are embedded. For example, mucosal or epithelial receptors in different regions of the ruminant gut can detect changes in acidity, monosaccharides, amino acids, hypo- and hypertonic solutions, as well as being mechanically sensitive (Harding and Leek 1972a).

C. Alimentary Enteroceptors

Detailed accounts of the behavior of alimentary sensory receptors in ruminants are available (Iggo 1966; Iggo and Leek 1967a; Iggo and Leek 1970; Leek 1972a; Leek 1977; Leek 1986; Leek and Harding 1975; Titchen 1968). A summary of some general and unresolved features of alimentary receptors follows. Electrophysiological evidence demonstrates that the sensory apparatus that detects changes in meal and digesta size and composition is situated in the different anatomical layers of the alimentary canal.

1. Mucosa, epithelia and submucosa

Highly sensitive mechanoreceptors with chemosensitive properties and discrete receptive fields are found. Fine unmyelinated nerve fibers, which may have a sensory function, are found in conical papillae of the reticular ridge of sheep (Leek 1972b). Because isocaloric meals of starch and glucose have similar effects on gastric emptying in man, although they have different osmotic potentials (Hunt and Knox 1968), osmoreceptors may be located close to the brush border of the intestine, because starch must first be hydrolyzed by pancreatic amylase enzyme. In the reticulorumen, the evidence suggests that epithelial receptors are both osmo- and mechanosensitive and that specific populations registering extremes of osmolality are absent. After making certain assumptions about chemical diffusion characteristics and impulse activation latency, the receptor activated by titratable acidity may be located 250 μm beneath the reticulorumen epithelial surface (Leek and Harding 1975). In the duodenum and abomasal antrum, acid receptors may be protected by a surface mucus barrier that alters the latency of the sensory (Cottrell and Iggo 1984c) and reflex response (Rose et al. 1977). Acid receptors may titrate Pco2 (Hunt and Knox 1968). How mucosal receptors may retain mechanosensitivity while becoming refractory to chemical solutions (Cottrell and Iggo 1984c) is unresolved.

2. Muscularis externa

Mechanoreceptors are intimately involved with active and passive forces generated in the alimentary wall. Evidence indicates an association with particular muscle sheaths and sphincters. In nonsphincteric areas, muscle mechanoreceptors are in series tension receptors. There is indirect (Iggo and Leek 1967c) but no direct evidence for different populations with high or low thresholds; they are involved in reflex regulation of motility and, via vagal pathways, in food intake (Jeanningros 1984). Neuroglial (hybrid) cells, located between the inner dense cells and outer, larger, smooth, circular muscle cells of circular muscle and closely associated with nerve axons, may function as tension receptors in the dog (Daniel 1977).

3. Serosa and mesentery

Mechanically sensitive serosal and mesenteric enteroceptors have multiple receptive fields that project segmentally along splanchnic pathways (Morrison 1977). This class of receptor may be activated in high-threshold reflex pathways, although single-unit analysis indicates a high mechanical sensitivity. Axonal-ligating and transport-blocking techniques have established peptide coexistence in vagal afferent fibers in all species studied. Peptides are transported toward enteroceptor terminals, and their function is unknown.

The work concerning ruminant enteroceptors is summarized in Table 1. Three electrophysiological approaches have been used: single-unit dissection; cross-reinnervation; and microelectrode penetration. Each technique offers both advantages and disadvantages. The major disadvantage of the dissection and microelectrode studies is the use of acutely anesthetized preparations. With cross-reinnervation there are problems of interpretation because of the plasticity of the regenerating process in semi-denervated tissues. Thus no preparation has been devised in which the sensory mechanism is unaffected. The influence of luminal stimuli on motility patterns must involve an activation of these alimentary enteroceptors. The electrophysiological evidence suggests a fine sensitivity of sensory receptors with projecting afferent axons. We do not yet know exactly the role played by individual receptors in activating reflex responses. They must monitor and modify the progress of the meal or chyme through the alimentary canal. We must therefore consider the evidence from studies using reflex mechanisms in order to try to understand their possible role (Table 2).

Table 1

Ruminant Gastrointestinal Sensory Receptors

c unmarked: acute electrophysiology nerve dissection; * chronic cross-reinnervation muscle EMG (2,7,8,9,24); ˆ acute nodose microelectrode study (6); and # includes anatomical detail (21,29).

aNerves: V: trigeminal; X: vagus; Sp: splanchnic; M: mesenteric.

b(1) Carr et al. (1987); (2) Falempin and Rousseau (1984); (3) Iggo and Leek (1967a); (4) Harding et al. (1978); (5) Storey and Johnson (1975); (6) Falempin et al. (1978); (7) Falempin and Rousseau (1983); (8) Rousseau (1984); (9) Rousseau and Falempin (1979); (10) Crichlow and Leek (1981); (11) Dalai et al. (1988); (12) Harding and Leek (1972a); (13) Harding and Leek (1972b); (14) Harding and Leek (1972c); (15) Iggo (1954); (16) Iggo (1955); (17) Iggo (1956a); (18) Iggo (1956b); (19) Leek (1967); (20) Leek (1969); (21) Leek (1972b); (22) Leek et al. (1976); (23) Leek et al. (1978); (24) Rousseau and Falempin, (1984); (25) Salmin (1960); (26) Cottrell and Iggo (1984a); (27) Floyd and Morrison (1974); (28) Cottrell (1984); (29) Cottrell and Greenhorn (1987); (30) Cottrell and Iggo (1984b); (31) Cottrell and Iggo (1984c); (32) Iggo (1966); (33) Iggo and Leek (1970); (34) Leek (1972a); (35) Leek (1977); (36) Leek (1986); (37) Leek and Harding (1975); (38) Titchen (1968)

Table 2

Influence of Gut Luminal Stimuli on GI Tract Motility

a+: excitation; –: inhil jition; ?: unclear; and 0: no effect.

II. CNS-Mediated Responses

Evidence for the involvement of extrinsic parasympathetic or sympathetic pathways in response to luminal stimuli has been obtained by electrophysiological recording of afferent and efferent nerve activity and by the effects on reflexes of nerve section. The latter studies must be interpreted with caution because, with the possible exception of selective nodose deafferentation, nerve section removes both afferent and efferent fibers; any loss or alteration in sensitivity of motility response could result from the absence of sensory or motor supply in dependent compartments, rather than indicate an extrinsic reflex control. For this reason, information regarding control of reticulorumen contractions comes mainly from electrophysiological recordings. The use of selective vagal deafferentation (Falempin and Rousseau 1979) may be extended to other systems.

A. Stimuli to Buccal Cavity and Esophagus

In decerebrate sheep and goats, tactile stimulation and distention of the terminal esophagus are effective stimuli for initiation of reticulum and rumen contractions (Titchen 1958, 1960). It is not known if these stimuli induce receptive relaxation of the abomasal body similar to their effects in animals with simple stomachs, but they do induce secondary esophageal peristalsis by a vago–vagal reflex (Falempin and Rousseau 1984) as in other species. These same stimuli (Ash and Kay 1959) plus mechanical stimulation of the oral mucous membranes (Borgatti 1947) also increase the frequency of primary reticulorumen contractions in conscious sheep. The trigeminal nerves carry the afferent signals from the buccal cavity. Many of these sensory nerves appear to be tonically active (Carr et al. 1987) and responsible for the increase in forestomach motility with feeding (Lead et al. 1984; Ruckebusch and Kay 1971), as their section reduces the frequency of primary contractions and abolishes the feeding response (Borgatti and Matcher 1958). In contrast, the feeding response remains after selective vagal deafferentation, but distention-induced (secondary) esophageal peristalsis is severely inhibited (Falempin et al. 1986; Falempin and Rousseau 1979).

There is little evidence in ruminants that chemical stimulation of the buccal cavity alone normally affects esophageal closure mechanisms. The nature of the diet affects the degree of motility increase during feeding by a mechanism involving the palatability of the food (Reid 1963). Nevertheless, motility can be manipulated pharmacologically with some oral chemical stimuli. Oral administration of 10% CuSO4 or some salt solutions transiently abolishes rumen and omasal motility and severely inhibits reticular motility while activating the esophageal groove reflex (Tsiamitas and Brikes 1981). Similar changes in motility are seen during natural closing of the groove (cephalic stimulus) in suckling calves (Kay and Ruckebusch 1971).

B. Stimuli to Reticulorumen

The influence of luminal stimuli to the reticulorumen on reticulorumen reflex motility has been thoroughly investigated; less clear, in most instances is whether these stimuli also directly affect motility elsewhere in the GI tract. All effects appear, at least partly, to be mediated via vago–vagal reflex. The distribution of vagal fibers is not uniform. There is a preponderance of innervation of the esophageal groove, reticulum, middle rumen wall, and omasal pillar (Morrison and Habel 1964). The primary and secondary contractions of the reticulorumen are extrinsically mediated contractions, as they depend entirely upon a vagal motor supply (Duncan 1953; Gregory 1984; Iggo and Leek 1967b; Rousseau 1984). They continue when the vagal afferent supply is removed, but the efferent supply is retained (Falempin and Rousseau 1979). In this preparation, the frequency of primary contractions is initially reduced by 20%, suggesting that there is a tonic afferent input with excitatory reflex effects from the vagi (Falempin and Rousseau 1979).

1. Distention

Reticular distention is a powerful excitatory stimulus for reticular (Titchen 1958) and primary rumen contractions (Titchen 1960) in decerebrate sheep and goats, and in sheep anesthetized with halothane (Leek 1969). However, high reticular pressures inhibit secondary rumen contractions in decerebrate (Reid and Titchen 1965) and anesthetized sheep (Leek 1969). Stretch of the reticulorumen fold is a particularly potent stimulus to reticuloruminal contractions in decerebrate sheep (Titchen 1960). In conscious sheep, stretch of the reticulorumen fold has more variable effects on existing contractions, whereas stretch of the reticulo-omasal orifice regularly increases the frequency of reticular contractions (Ash and Kay 1959), and both stimuli induce rumination behavior (Ash and Kay 1959).

Gaseous insufflation of the rumen increases the frequency of secondary ruminal contractions and eructation in cattle (Stevens and Sellers 1959) and sheep (Louvier et al. 1979, Weiss 1953) in proportion to ruminal pressure; the frequency of primary contractions in sheep also increases linearly up to a ruminal pressure of 10 cm H2O, but is suppressed at higher pressures (Louvier et al. 1979), while in cattle the frequency is little affected (Stevens and Sellers 1959). At higher ruminal pressure (>14 cm H2O), the force of reticulum and rumen contractions is also reduced in decerebrate sheep (Reid and Titchen 1965).

It has been generally concluded that the frequency and amplitude of secondary ruminal contractions are principally determined by the level of ruminal distention (Stevens and Sellers 1959); chemical and tactile stimulation are less potent. The response to distention may also depend to a small extent upon the chemical nature (i.e., CO2 content) of the distending gas (Louvier et al. 1979); however, most studies have found no difference in the effect of a variety of distending gases (Reid and Titchen 1965). The exact location that initiates secondary contractions has proved somewhat controversial, but it now seems possible that the effect follows excitation of the slowly adapting mechanoreceptors located in the cranial sac (Leek 1969). Interestingly, it has similarly been shown that the frequency of B contractions in the llama is directly dependent upon the degree of distention of the cranial sac (Gregory et al. 1985).

Although ruminal and reticular distention have profound effects upon reticuloruminal motility, removal of their contents has no effect on the frequency of primary cycle contractions, and even secondary contractions continue, albeit at a reduced amplitude and frequency (Ash 1959; Stevens and Sellers 1959), showing that baseline motility is not critically dependent on distention with ingesta in that compartment.

Distention of the rumen also markedly increases motility of the cecum and proximal colon in the sheep (Fioramonti and Ruckebusch 1979)—other areas of the GI tract have not been investigated. The response might perhaps be compared to the so-called gastrocolic reflex in animals with simple stomachs. The effect is blocked by reversible vagal anesthesia (Fioramonti and Ruckebusch 1979), indicating a vagally mediated component.

2. Tactile stimulus

Gentle stroking of the epithelium of the reticulo-omasal orifice, reticulum, reticuloruminal fold, and esophageal groove increases the frequency of reticular contractions, induces rumination, and increases parotid secretion in conscious sheep (Ash and Kay 1959). Similar stimulation of other areas is generally ineffective. In cattle, the most sensitive region appears to be around the cardia, where stroking increases the frequency of primary cycle and secondary ruminal contractions (Stevens and Sellers 1959). The effects are presumed to occur via vago–vagal reflexes following activation of the rapidly adapting epithelial receptors located in these areas of the reticulorumen (Harding and Leek 1972b; Leek and Harding 1975). The presence of liquid in the area of the cardia prevents opening of the cardia and subsequent eructation, even when the secondary ruminal contractions continue to be initiated (Dougherty et al. 1958); this reflex is probably important in the onset of bloat. So-called eructation-inhibition receptors, which could induce such a response, have yet to be identified.

3. Chemical stimuli

Reticuloruminal motility is inhibited by ruminal infusion of volatile fatty acids (VFA) (butyrate > propionate acetate); the degree of inhibition depends upon the concentration of undissociated VFA present, rather than the total concentration of VFA in both its forms or the pH per se (Ash 1989; Gregory 1987; Upton et al. 1977). Reticuloruminal motility is also inhibited by undissociated lactic acid, with a potency similar to acetate (Gregory 1987). Inhibition seems to affect mainly contraction amplitude, although frequency is also affected; primary rumen contractions may be more readily inhibited than secondary contractions, the overall degree of inhibition depending upon the additive effect of all undissociated VFA and lactate in the rumen (Gregory 1987). Inhibition is rapid after the introduction of VFA into an experimentally emptied rumen, especially as VFA vapor (Ash 1959), and is not prevented by section of splanchnic nerves (Ash 1959) or injection of α- or β-adrenergic blockers (P. C. Gregory, unpublished); moreover, ruminal liquor that inhibits motility excites the vagally innervated reticuloruminal epithelial receptors (Crichlow and Leek 1981). Therefore it is generally concluded that inhibition of motility is via a vago–vagal reflex following excitation of these receptors (Leek 1986).

There is a dense population of epithelial receptors in the reticulum (Harding and Leek 1972b). However, when VFA are infused, either into the rumen or directly into the reticulum, motility of both compartments appears to be inhibited according to the ruminal rather than the reticular concentration of undissociated VFA. Therefore rumen receptors appear to be more important than reticular receptors in causing inhibition; perhaps overall, there are more rumen receptors, which are more sparsely dispersed or have different thresholds. On the other hand, if inhibition is purely via a vago–vagal reflex, motility might be expected to restart immediately after rumen washout and replacement of original rumen contents. However, motility restart is very variable, e.g., from 0 to 57 min (Gregory 1987). Furthermore, the rumen VFA concentrations necessary to inhibit appear to be varied by other factors which include fasting (Leek et al. 1976). Although the epithelial receptors are excited also by hypo- and hyperosmolar solutions (Leek and Harding 1975), rumen motility is unaffected by raising and maintaining the ruminal osmolarity to 420 mOsm/kg−1 for 6 hr (P. C. Gregory et al., unpublished) or even when osmolarity is raised to 600 mOsm/kg−1 for short periods. Such changes do, however, considerably inhibit food intake (Ternouth and Beattie 1971), suggesting that osmotic stimuli are more important for control of food intake than gut motility. It is still unexplained how tactile stimulation of sensory receptors excites contractions, yet chemical stimulation of the same receptors inhibits motility. It therefore seems likely that other factors may also contribute to the inhibition by VFA as discussed later (p. 23).

C. Stimuli to Omasum

Despite its anatomically strategic position, the omasum does not appear to play an important or active role in the control of GI-tract motility. In decerebrate sheep, distention of the omasal canal increases the force and frequency of reticular contractions (Titchen 1958), while squeezing the omasum also induces reticular contractions associated with swallowing movements (Titchen 1958). By contrast, in conscious sheep, distention of the omasal canal inhibits reticular contraction frequency, increases motility of the omasal body, and possibly induces secondary rumen contractions, but does not affect abomasal motility (Bueno 1975); distention of the comparable region of the llama produces similar results (Gregory et al. 1985). In cattle, in which the omasum is relatively larger than in the sheep, moderate distention of the omasum slows or accelerates and increases the amplitude of reticular contractions, while intense distention inhibits reticular and ruminal contractions (Ruckebusch and Kay 1971). The mechanisms involved have yet to be investigated. Creation of a reticuloabomasal anastomosis, which allows direct digesta transit from the cardia to the abomasum, thus bypassing the omasum, virtually abolishes rumination (Laplace 1970). It has therefore been suggested that the omasum may have a regulatory role in rumination behavior, but the mechanism of this effect remains to be clarified.

D. Stimuli to Abomasum

1. Distention

Graded abomasal distention inhibits the frequency and amplitude of primary reticuloruminal contractions in decerebrate sheep (Titchen 1958), conscious sheep (Gregory 1984; Phillipson 1939) and cattle (Ruckebusch and Kay 1971), but has little effect, or even stimulates secondary ruminal contractions and inhibits the force of omasal body contractions (Gregory 1984). Abomasal distention seems to be the cause of the delayed emptying and inhibition of reticuloruminal motility after sucking in milk-fed calves (Kay and Ruckebusch 1971). In goats (Ehrlein and Hill 1970) and cattle (Stevens et al. 1960), the inhibition of omasal body motility appears to be the most sensitive response. In some studies abomasal distention stimulates reticular contraction frequency with a decrease in amplitude of primary ruminal contractions; the exact conditions for this response are not clear, but it seems to occur most often with low levels of distention in fasted animals. By comparison, in the llama, distention of the hind stomach generally causes an initial stimulation followed by inhibition of forestomach motility (Gregory et al. 1985). In the sheep, the effects of forestomach motility, at least, depend upon the balance between vago–vagal and splanchno–vagal reflexes. After cutting the splanchnic nerves, abomasal distention increases the frequency of primary contractions with either an increase or a decrease in contraction force, by vago–vagal reflexes (Titchen 1958).

Until recently it has not been clear to what extent abomasal motility is affected by abomasal distention. Abomasal motility does not appear to alter with the size of the milk meal (1–4 liters) in preruminant calves (Bell and Watson 1976), but in goats, increasing the abomasal volume by 0.3 to 0.6 liters generally increases contraction amplitude (Ehrlein and Hill 1970). In food-deprived sheep, the amplitude of abomasal contractions falls with a reduction in abomasal volume (Gregory et al. 1985). In the cat, gastric antral distention to 5–10 cm H2O causes adaptive relaxation of the corpus and fundus by vago–vagal (Abrahamson 1973) and vago–splanchnic reflexes (Abrahamson 1974), while distention of the corpus of the transected ferret stomach stimulates antral motility by a vago–vagal reflex (Andrews et al. 1980). As the rate of abomasal emptying in preruminant calves varies with the volume of the meal (Bell and Watson 1976), in exactly the same manner as in animals with simple stomachs, (Hunt and Knox 1968), similar mechanisms may also be present in ruminants. Abomaso–abomasal reflexes have been studied in the anesthetised sheep with the abomasum divided into separate compartments by transverse section (D. F. Cottrell and H. G. Stanley, in preparation). Excitation of in series tension receptors of the abomasal antrum (D. F. Cottrell and G. W. Reynolds in preparation) initiates a vagally dependent contraction-to-contraction inhibition of motility in the abomasal body. Duodenal tension receptors also produce inhibition of motility of the abomasal body but not the antrum. A vagally mediated feed-forward excitation of antral motility by contraction of the abomasal body is also present. These mechanisms would play a role in creating pressure gradients across the abomasum and the abomaso-duodenal junction to allow aboral movement of chyme. However, it has recently been suggested that the local nerve supply may not be so important as the physical constriction of the pyloric sphincter (Mabert and Ruckebusch 1989) in controlling abomasal emptying.

2. Chemical stimuli

Acidification of the abomasum to pH lower than 1.0 with HCl or H2SO4 elicits reticulum contractions in decerebrate sheep and goats (Titchen 1958), and this effect was originally thought to provide an important excitatory input to the gastric centers. However, mean abomasal pH is generally maintained greater than 2 : 0 (Hill 1968); therefore, this effect would have physiological significance only if the receptors lie close to the acid-secreting cells. In sheep anesthetised with halothane, abomasal acidification to pH 1.0 is effective only in 30% of sheep, and then produces only increased contraction strength with no effects on frequency (Iggo and Leek 1967c).

Abomasal infusion of VFA or lactic acid also increases the frequency and/or amplitude of reticular contractions (Ash 1959; Gregory 1987) together with an inhibition of the amplitude of primary rumen contractions (Gregory 1987). These effects were seen only with abomasal concentrations above 60–70 mmol/liter, and because abomasal VFA concentrations are generally less than 25 mmol/liter (Gregory and Miller 1989), such effects may have limited physiological significance unless sensory receptors are located near the omaso-abomasal orifice. Receptor excitation may occur during ruminal lactic acidosis (Dunlop and Hammond 1965). The effect of abomasal infusion of VFA, HCl, NaCl, and lactate appear to be identical (P. C. Gregory, unpublished). As tactile stimulation of the abomasal mucosa also stimulates reticular contractions (Titchen 1958), and the effects are abolished by section of the abomasal branch of the ventral abdominal vagus (Titchen 1958), it is likely that the effects are via vago–vagal reflex following excitation of the abomasal mucosal receptors (Leek 1977). Abomasal infusion of VFA also inhibits abomasal motility (Bolton et al. 1976); however, as inhibition is not observed until 5–20 min after the end of infusion, it is unclear whether the effects arise from direct abomasal stimulation or after passage into the duodenum (Gregory 1987; Gregory and Miller 1989), or are humoral in mechanism, or involve hepatic enteroceptors.

E. Stimuli to the Small Intestine

Many studies in the ruminant have investigated the application of stimuli to the duodenum only, and the influence of similar stimuli elsewhere in the small intestine have been largely ignored. In animals with simple stomachs, responses to many stimuli are elicited from other sites throughout the small intestine. Owing to the considerable digestion and absorption of nutrients proximal to the duodenum in the ruminant, the regulatory role of the duodenum may be less than in animals with simple stomachs (Nicholson and Omer 1983). Nevertheless it has been demonstrated that the duodenum possesses considerable capacity to regulate GI-tract motility in the ruminant. Although luminal stimuli to the duodenum appear to be mainly concerned with control of abomasal motility and outflow, as a general rule (Gregory and Miller 1989) the same stimuli, but at higher threshold values, also affect reticuloruminal motility, and some also affect small-intestinal motility.

1. Distention

Duodenal distention in goats, by rapid infusion of saline (30 ml/min), strongly inhibits abomasal and omasal motility, increases pylorus tone, and slightly inhibits reticular contraction frequency (Ehrlein and Hill 1970). The mechanisms responsible have not been extensively studied in sheep. In animals with a simple stomach, inhibition of gastric motility by duodenal distention is reduced by vagotomy or pharmacological sympathetic blockade (Daniel and Wiebe 1966). The vagal motor supply is altered in the dog by a reduction in firing of vagal excitatory fibers and an increase in firing of vagal inhibitory fibers (Miolan 1985); however, the most important response seems to be alteration in sympathetic discharge, causing presynaptic noradrenergic inhibition of enteric cholinergic neurons (Jansson and Lisander 1969). This effect occurs at physiological levels of distention.

2. Chemical stimuli

Duodenal infusion of HCl is a potent stimulus in ruminants and animals with simple stomachs. Inhibition of abomasal motility and outflow occurs in the preruminant calf (Bell and Mostaghni 1975) and adult sheep (Gregory and Miller 1989) according to the amount of HCl delivered to the small intestine (Bell et al. 1981). In sheep, the threshold dose to inhibit abomasal motility is duodenal infusion of about 12.5 mmol HCl/hr−1 (Gregory and Miller 1989). At higher rates of infusion (30 mmol/hr−1) abomasal motility is abolished, and the frequency and amplitude of reticuloruminal contractions is severely reduced (Gregory and Miller 1989; Gregory et al. 1984), while rapid injection of 1 mmol HCl induces a premature duodenal phase III (Gregory et al. 1984). Nevertheless, it is doubtful whether any of these effects are physiological; the lowest effective dose of HCl is approximately double the usual rate of gastric acid production (Hill 1960), which is normally tightly controlled (Hill 1968). Moreover, there is no correlation between abomasal acid secretion and duodenal migrating myoelectric complex (MMC) (Gregory et al. 1984).

Duodenal infusion of NaHCO3, sufficient to neutralize the chyme leaving the abomasum, does not alter abomasal motility or outflow, reticuloruminal motility or MMC frequency (Gregory and Miller 1989; Gregory et al. 1984). However, increasing the duodenal luminal NaHCO3 concentration still further, sufficient to excite the duodenal alkali receptors in sheep (Cottrell and Iggo 1984c), stimulates abomasal motility (Bell and Grivel 1975) and emptying (Bell and Mostaghi 1975) in calves. The mechanisms responsible for the effects are probably similar to those described in animals with a simple stomach.

In the dog, duodenal HCl has been shown to inhibit gastric motility by a vago–vagal reflex (Miolan 1985), but principally by a reflex involving the sympathetic nerves (Cooke and Clarke 1956). In preruminant calves, the stimulation of abomasal motility and emptying with duodenal NaHCO3 is abolished by vagotomy, but the HCl inhibition of abomasal motility and emptying is not significantly affected by bilateral vagotomy or splanchnectomy (Bell et al. 1981). Involvement of a purely peripheral autonomic reflex via the prevertebral ganglia was not investigated. Vagotomy severely inhibits abomasal emptying, making it difficult to be certain that vagotomy does not influence the response to HCl inhibition. In sheep vagotomy reduces, but does not abolish, the HCl inhibition of abomasal motility, but does abolish the premature duodenal phase III (Gregory et al. 1984). Other possible mechanisms for the HCl effects are discussed below.

Duodenal infusion of VFA or lactic acid inhibits abomasal motility and outflow in calves (Bell and Grivel 1975; Bell and Mostaghni 1975), goats (Ehrlein and Hill 1970) and sheep (Gregory and Miller 1989). In sheep the threshold value is an infusion rate of 24 mmol hr−1, which was estimated to raise the duodenal concentration to 35 mmol/liter (Gregory and Miller 1989). These high concentrations may perhaps be reached in pathological states such as ruminal lactic acidosis (Dunlop and Hammond 1965) but are not normally approached in roughage-fed sheep (Hogan and Weston 1967), or even in concentrate-fed sheep in which levels up to 24 mmol/liter are recorded (Hill 1960). At higher (approximately double) concentrations, the frequency and amplitude of primary and secondary forestomach contractions are inhibited (Gregory 1987). These effects may involve reflexes following excitation of the VFA-sensitive mucosal receptors in the duodenum (Cottrell and Iggo 1984c) or putative receptors in the hepatic-portal circulation (Anil and Forbes 1988).

Vagotomy reduces or abolishes the inhibition of gastric motility by duodenal glucose, fat, or fatty acids in pigs (Rose et al. 1977) and dogs (Cooke and Clarke 1956). In ruminants, duodenal infusion of emulsified fat or oleic acid strongly and rapidly inhibits abomasal motility and outflow (Ehrlein and Hill 1970; Gregory and Miller 1988; Titchen et al. 1966), together with an increase in pyloric tone (Ehrlein and Hill 1970) similar to their effects in animals with simple stomachs. The threshold dose in sheep is equivalent to a duodenal flow of about 5 g fat/hr−1 (Gregory and Miller 1989), a level that might be reached in adult sheep with a diet supplemented to contain 9–10% fat. Surprisingly, even in milk-fed calves, the response does not appear to have much physiological significance, as increasing the fat content of the milk up to 17% has little effect on abomasal emptying (Ash 1964).

Gastric emptying in man is partly regulated by duodenal osmolarity (Hunt and Knox 1968) and delivers a constant rate of calories to the duodenum (McHugh and Moran 1979). Abomasal emptying in preruminant calves can be similarly regulated by duodenal osmolarity, i.e., stimulated by hypotonic and inhibited by hypertonic solutions (Bell and Mostaghni 1975; Bell et al. 1981), but there does not appear to be a direct influence of the energy content of duodenal chyme (Bell and Webber 1976). Nevertheless, glucose appears to exert specific (i.e., independent from osmolarity) but relatively weak effects to inhibit abomasal motility and outflow in calves (Bell and Mostaghni 1975) and sheep (Gregory and Miller 1989), and also to inhibit reticuloruminal and small intestinal motility (Gregory and Miller 1989). The threshold dose in sheep is reached with a duodenal flow of about 16 g/hr−1, or a concentration of about 150 mmol/liter (Gregory and Miller 1989), levels unlikely to be reached even in sheep eating a rich grain diet, and far above the concentration used to test for the presence of glucoreceptors in the duodenum (Cottrell and Iggo 1984c). Even though no vagal receptors sensitive to osmolarity (range 20–1500 mOsm/kg−1) have yet been observed in the duodenum (Cottrell and Iggo 1984c) vagotomy reduces the inhibition of abomasal motility by hypertonic NaCl and abolishes the induction of premature phase III (Gregory et al. 1984), suggesting that there may be vagal enteroceptors sensitive to hypertonic NaCl. Perhaps these could be located more distally, in the jejunum or in the hepatic circulation. Alternatively, there is evidence in other species that osmotic effects may be mediated via the prevertebral ganglia, in which case the local nerve-recording technique ought to have identified them.

Duodenal infusion of protein hydrolysate has inconsistent effects on abomasal motility in goats (Ehrlein and Hill 1970; Singleton 1951). In sheep infusion of 6 g/hr−1 (5 ml/min−1 2% peptone), a quantity calculated to increase duodenal flow of nitrogen by 22%, reduces abomasal outflow by 19%. Obvious inhibition of abomasal motility is not seen until infusions of 12 g/hr−1 peptone are used, while at still higher infusion rates (6.5 ml/min−1 4% peptone) reticuloruminal motility is also inhibited without affecting small intestinal motility (Gregory and Miller 1989). Thus peptone may play an important physiological role in the control of abomasal outflow (Van Bruchem et al. 1984). There is as yet no evidence concerning the mechanisms involved.

In the cat, intestinal chemoreceptors sensitive to amino acids are described (Jeanningros 1982). In sheep, duodenal receptors sensitive to tyrosine and tryptophan are reported (Cottrell and Iggo 1984c). Tryptophan is known to inhibit abomasal motility and outflow in calves (Bell and Webber 1979) and sheep (Gregory and Miller 1989). However, the effects require high doses (threshold of 4 g/hr−1 in sheep) which also inhibit reticuloruminal motility and, unlike protein infusion, stimulate duodenal motility and induce a premature duodenal phase III (Gregory and Miller 1989).

Lastly, duodenal infusion of KCl solutions inhibits abomasal motility and outflow in calves (Bell and Mostaghni 1975) and sheep (Gregory and Miller 1989). A 38% increase in duodenal K+ concentration (to 58 mmol/liter) causes a 13% reduction in abomasal outflow in sheep, while faster infusions also inhibit reticuloruminal motility (Gregory and Miller 1989). Because ruminal K+ levels above 100 mmol/liter are reported in sheep feeding on heavily fertilized grass, and as less than 10% of dietary K+ and about 13% of the water is absorbed in the omasum, it is possible that these levels are reached in the duodenum. The effect may be mediated via activation of the KCl-sensitive receptors in the duodenum (Cottrell and Iggo 1984c).

In the cat, duodenal infusion of cold (10–12°C) or warm (46–49°C) solutions inhibits antral motility; the effects are unaffected by splanchnotomy but are abolished by vagotomy (El Ouazzani and Mei 1979). Such studies have not been made in ruminants. Compression-insensitive thermoreceptors are found in the duodenum of sheep, and tension receptors are thermomodulated (Cottrell 1984).

F. Stimuli to the Ileum

A variety of luminal stimuli to the ileum can alter GI-tract motility in animals with a simple stomach. In humans, ileal infusion of lipids or proteins slows gastric emptying and/or slows transit through the small intestine (Read et al. 1984), while volatile fatty acids stimulate ileal motility (Kamath et al. 1988). Comparable studies have not been made in ruminants. An ileocecal reflex is seen in sheep (Fioramonti and Ruckebusch 1979). In the caecum, a recurrent phase of hyperactivity followed by a phase of inactivity relates closely to the occurrence of phase III activity in the terminal ileum. Cecal hyperactivity can be experimentally induced by ileal, but not cecal, infusion of saline, and so probably results from the rise in flow of digesta in the terminal ileum, which is maximal just before a phase III (Bueno and Fioramonti 1979). As the reflex is also observed in an isolated cecal pouch, it appears to depend upon extrinsic rather than intrinsic nervous pathways.

G. Stimuli to the Large Intestine

Few studies have been performed with luminal stimuli to the large intestine of ruminants, and little is known of the mechanisms responsible for the effects that have been reported.

Distention of the cecum inhibits primary reticuloruminal contractions without affecting secondary rumen contractions (Weiss 1953); this effect is similar to that of abomasal distention and may involve similar mechanisms. The level of cecal distention is also an important regulator of cecal motility (Fioramonti and Ruckebusch 1978); localized and coordinated contractions require a threshold pressure of 5 cm H2O. It is not known whether intrinsic or vago–vagal reflexes are involved, but vagotomy initially greatly inhibits transit through the large intestine in calves (Bell et al. 1977).

Cecal infusion of 10 mmol undissociated VFA inhibits cecal motility by over 50% (Svendsen 1972), and may contribute to the decrease in cecal motility in cattle changed from hay to a high-grain ration (Svendsen and Kristensen 1970), in which a rise in cecal VFA is observed. The mechanism has not been studied but bears obvious resemblance to VFA effect in the reticulorumen. Cecal inhibition occurs in the order butyrate > proprionate acetate, as in the rumen, but at apparently lower physiological VFA concentrations.

A reflex presumed to be present in ruminants, as in other animals, is the coordinated contraction of colon and rectum following their mechanical stimulation, especially in the presence of light distention. This reflex is thought to be important in initiating defecation and, as shown by direct neural recording and nerve section in the cat, is mediated via the sacral parasympathetic nerves (Groat and Krier 1979).

III. Spinal Reflex Mechanisms

Intestinal distention (or mucosal irritation) reflexively inhibits motility of the small and large intestine in animals with simple stomachs, i.e., the intestino–intestinal, intestino–colic, and colono–colic reflexes. It seems probable that such reflexes exist also in ruminants, although none has yet been described. They involve two different but interconnected pathways, the longer spinal reflex and a shorter peripheral pathway through the prevertebral ganglia (Furness and Costa 1987).

The spinal reflex involves at least one spinal interneuron, and because transection of the cervical cord reduces intestinal motility and the threshold of pressure needed to evoke the reflex, it may be concluded that descending pathways exert a tonic restraint on the reflex (Johansson et al. 1968). It has been suggested that the spinal reflex is a low-threshold and the prevertebral reflex a high-threshold pathway (Furness and Costa 1987). However, the relative significance of these two pathways remains a matter of controversy, as the prevertebral ganglia reflex operates in the guinea pig colon at low physiological pressures of 5 to 10 cm H2O (Kreulen and Szurszewski 1979).

IV. Peripheral Reflexes via the Prevertebral Ganglia

It is now established, using in vitro preparations with gut segments connected only via the prevertebral ganglia, that there are peripheral intestinal reflexes mediated via the prevertebral ganglia (Kreulen and Szurszewski 1979). The pathway consists of an afferent fiber from a myenteric sensory neuron, which synapses with the cell body of an efferent noradrenergic neuron in the prevertebral ganglia; this sympathetic neuron terminates within the myenteric plexus. In the rabbit, the mesenteric nerves from the small intestine contain about 30% of afferent axons from the myenteric ganglia (Ross 1958). In the guinea pig, these axons provide synaptic input to the celiac ganglion after distention of the colon in an in vitro system (Kreulen and Szurszewski 1979).

The prevertebral pathway may also play a role in the inhibition of antral motility and aboral inhibition of intestinal motility after stimulation with duodenal or jejunal acid and jejunal hypertonic infusions in the dog (Furness and Costa 1987); at least part of the reduction in response after vagotomy could be an indirect effect due to lowering of cholinergic tone, reducing the effectiveness of noradrenergic activation (Furness and Costa 1987). As the responses to duodenal HCl and hypertonic NaCl are still observed in sheep after vagotomy (Gregory et al. 1984), and to HCl in calves after vagotomy with lumbar splanchnotomy (Bell et al. 1981; Bell et al. 1977), it seems probable that prevertebral mechanisms are involved in the ruminant.

V. Intrinsic Reflexes via the Enteric Nervous System

The role of the enteric nervous system in responses of the ruminant GI tract to luminal stimuli is in most cases largely a matter of conjecture, based on responses observed after vagotomy or compared with similar responses in other species.

A. Reticulorumen

As previously discussed, the primary and secondary contractions of the forestomach are dependent upon a vagal motor supply and are largely controlled via vagovagal reflexes (Iggo and Leek 1967b; Iggo and Leek 1967c; Leek 1986). However, chronically vagotomized sheep, provided with intragastric nutrition, develop coordinated contractions, which occur almost simultaneously over the whole reticulorumen (Gregory 1984). These contractions are unaffected by splanchnotomy and are blocked by hexamethonium or atropine, or by lowering the rumen temperature to 30°C, and are evidently initiated by the myenteric plexus (Gregory 1984). In this preparation, the contractions at normal rumen volume show a minute rhythm similar to that of the small intestine (Bulbring 1962). Contraction frequency varies according to the level of rumen distention; i.e., contractions are absent below a threshold rumen volume and reach a maximum of 6 to 7/min−1 as volume as increased (Gregory 1982). Therefore it appears that within the intrinsic plexus there are tension-sensitive mechanisms resembling the myenteric neurons of the cat small intestine (Wood 1987). Although, in other species, sensory myenteric fibers are known to run in the mesenteric nerves, it has been reported that none enters the vagi (Habel 1956).

Any relationship between the vagal deep tension or slowly adapting mechanoreceptors (Hukuhara et al. 1958) and any myenteric tension receptors has yet to be established, but they evidently lie in a similar location within the wall of the reticulorumen and possess similar reflex properties. It is not clear if, or how, these sensory myenteric neurons play any role in the coordinated response of the extrinsically driven contractions to ruminal distention (could collateral fibers project centrally?) or whether they only affect the neurogenically mediated intrinsic contractions.

In addition, there are intrinsic myogenic reticuloruminal contractions, at a frequency of 10–12/min−1, which are unaffected by ganglion or muscarinic blockers (Leek 1985). These contractions may influence the extrinsic contractions as well. In anesthetised sheep, the frequency of the myogenic contractions increases with distention of the smooth muscles, and these intrinsic contractions also increase afferent vagal discharge of the in-series tension receptors (Leek 1969, 1985). These intrinsic local contractions are regularly seen only in conscious sheep after inhibition of extrinsic or neurogenic intrinsic contractions (P. C. Gregory, unpublished), and therefore their main importance may be to restore neurogenic contractions rather than to affect contractions already present.

It is possible that the inhibition of reticuloruminal motility by VFA could at least partly involve local neural reflexes. Ruminal VFA inhibit the neurogenically mediated intrinsic contractions of chronically vagotomised sheep (Gregory 1982). The effect could be a nonspecific effect, e.g., blocking neural transmission or activity of the tension-sensitive myenteric ganglia required for intrinsic motility (Gregory 1982) by their anesthetic properties (known for butyrate and proprionate but not for acetate). Alternatively it could indicate that there are VFA-sensitive myenteric neurons presumably with sensory nerve endings in the epithelial layer. In any event, the ruminal concentration of each individual undissociated VFA at the point of 50% inhibition and abolition of motility of extrinsically driven and intrinsic contractions are almost identical (Gregory 1987). It seems probable, therefore, that either similar mechanisms or receptors with similar properties are involved in the inhibition of the two types of contractions.

B. Omasum

Omasal contractions are initiated by the enteric nervous system (Bueno and Ruckebusch 1974). Stimulation of omasal body contractions by digesta and of omasal leaves by VFA are unaffected by vagotomy (Bueno and Ruckebusch 1974) and may be mediated via enteric neural reflexes.

C. Abomasum and Large Intestine

Abomasal VFA infusion inhibits abomasal motility in vagotomized sheep (P. C. Gregory, unpublished). The inhibition of cecal motility by cecal VFA (10 μmol/liter) may involve vago–vagal or enteric neural pathways. In rats, low doses of VFA (0.04–0.1 mmol/liter) stimulate colonic motility by an enteric reflex (Yajima 1985), and a similar mechanism may account for the stimulation of cecal motility by low doses of VFA (0.04 mmol) in the sheep (Svendsen and Kristensen 1970).

D. Small Intestine

It is widely recognized that the various motility sequences of the MMC of the small intestine may be modulated by extrinsic nerves and hormones. In ruminants, as in other animals, these are programed via the enteric nervous system (Bueno et al. 1979; Marik and Lode 1975). The enteric nervous system controls segmental contractions and peristalsis in the small and large intestine (Furness and Costa 1987). Localized distention causes oral excitation and aboral inhibition, the whole contraction–relaxation sequence being propagated in an oral to anal direction (Furness and Costa 1987). This propulsive reflex may be responsible for the duodenal rush seen in normal and vagotomized sheep; i.e., distention of the duodenal bulb (by duodenal infusion or by abomasal emptying) initiates a wave of peristalsis, which passes rapidly through the duodenum and often into the jejunum (P. C. Gregory and G. Wenham, unpublished). For this reason, also, it is likely that sensory receptors are located in the jejunum as well as the duodenum (Nicholson and Omer 1983).

An intrinsic reflex is also probably responsible for the increase in duodenal bulb motility and inhibition of jejunal motility following duodenal infusion of HCl or hypertonic NaCl observed before and after vagotomy in sheep (Gregory et al. 1984) and dogs (Furness and Costa 1987; Hukuhara et al. 1985; Thomas and Baldwin 1971). Because small intestinal motility is controlled mainly via the enteric nervous system, it is probable that the inhibition of small intestinal motility and changes in rate of transit with duodenal infusion of VFA (Gregory and Miller 1989) involve intrinsic pathways. Intrinsic mechanisms may also play a role when increases in volume of digesta entering the duodenum increase the level of phase II activity and rate of digesta transit through the small intestine in the sheep (Gregory et al. 1985).

VI. Humoral Mechanisms

There is no doubt that some luminal stimuli could affect GI motility by humoral mechanisms, but in many experimental cases it is likely this only happens with stimuli at pharmacological or pathological levels.

A. Stimuli to the Reticulorumen

Inhibition of reticuloruminal motility by ruminal infusion of VFA or during ruminal lactic acidosis could involve humoral factors in addition to the neural mechanisms previously discussed. Before abolition of motility with ruminal VFA infusion, there is a considerable rise in systemic levels of VFA, which can directly inhibit the gastric motor centers (Le Bars et al. 1954). After jugular infusion of VFA, reticuloruminal motility is considerably inhibited at systemic VFA concentrations similar to those causing abolition with ruminal infusions. This demonstrates the existence of a direct central effect of plasma VFA in addition to the neural inhibitory effect of ruminal VFA.

In addition, plasma insulin and glucagon levels rise sharply with ruminal infusions of butyrate and propionate (somatostatin levels have not been measured but might be similarly affected). Plasma glucose levels are generally also considerably increased before abolition of motility. Because these changes all inhibit forestomach motility (Bowen 1962; Vallenas 1956; P. C. Gregory, unpublished) they could add to the inhibitory potency of the VFA.

Two other chemical stimuli could inhibit motility by excitation of the vagal epithelial receptors (Leek and Harding 1975) or after absorption. The inhibition of motility after infusion with Na2CO3 was reported to mirror the systemic plasma acid–base changes rather than ruminal pH (Clark and Lombard 1951), and so could represent a direct effect on gastric motor centers. Ruminal infusion of NH3 inhibits forestomach motility (Bueno et al. 1977), an effect that may be involved with rumen paralysis seen in animals consuming diets high in urea (Lewis 1960), and also inhibits cecal motility (Fioramonti and Ruckebusch 1979) after a short period of hypermotility. The effects do not depend upon ruminal pH nor does systemic urea application mimic the effects, evidence which seems to indicate a site of action within the rumen. However, the effects could result from diffusion of NH3 into the peritoneal cavity (Chalmers and White 1969). Indeed intraperitoneal injection of NH3 exactly reproduces the changes in cecal motility caused by cecal or ruminal infusion of NH3, but with much shorter latency (Fioramonti and Ruckebusch 1979).

B. Stimuli to the Abomasum

There is some evidence for humoral mechanisms affecting motility from abomasal stimuli. A likely candidate is gastrin, which is released following gastric distention, but chiefly following gastric infusion of protein (Walsh 1987). Intravenous infusion of pentagastrin inhibits abomasal motility in calves (Bell and Watson 1977) and adult sheep (P. C. Gregory, unpublished), and in higher doses inhibits reticuloruminal motility (Grovum 1981) and excites duodenal tension receptors (Cottrell and Iggo 1984b). Gastrin could possibly be concerned with the inhibition of abomasal emptying with abomasal infusion of protein (Van Bruchem et al. 1984), but its major physiological role is in the control of abomasal acid secretion rather than with control of motility.

C. Stimuli to the Duodenum

There is good evidence that duodenal infusion of acid can produce humorally mediated motility effects. Humoral agents are indicated in the delayed excitation of duodenal tension receptors by 50 mmol HCl in sheep (Cottrell and Iggo, 1984a). The inhibition of abomasal and reticuloruminal motility in sheep by duodenal infusion of high doses of lactate (336 mmol/hr−1) are mimicked in a recipient sheep following transfusion of blood from the gastroduodenal vein of the infused sheep (Bruce and Huber 1973). Duodenal infusion of HCl causes release of secretin (Bell and Watson 1976) and somatostatin (Bell et al. 1981), and infusion of both these hormones inhibits abomasal motility (Bell et al. 1981; Bruce and Huber 1973; McLeay and Moran 1979). Secretin also inhibits reticuloruminal motility (Bruce and Huber 1973; Grovum 1981). Infusion of both secretin (Bueno and Fioramonti 1979) and somatostatin (P. C. Gregory, unpublished) also increases MMC frequency, an effect observed with high rates of HCl infusion (Gregory et al. 1984). In man, intraduodenal HCl causes motilin secretion, and this induces premature phase III activity (Walsh 1987), a mechanism that may be activated by HCl in sheep (Gregory et al. 1984). The loss of the response after vagotomy could indicate that motilin release requires a vagal component, because in dogs vagal stimulation induces motilin release (Lee et al. 1981), while somatostatin secretion, which could also mediate the response, is not blocked by vagotomy in the calf (Bell et al. 1981).

Duodenal infusion of fat or oleic acid has a biphasic effect: initially there is rapid inhibition of abomasal motility, and then after a latency of 20–30 min, inhibition of reticuloruminal motility (Gregory and Miller 1989). This suggests that there may be both neural and hormonal mechanisms involved. The infusions also disrupt or increase the frequency of the MMC and strongly reduce the level of phase II activity of the small intestine, together with a paradoxical increase in rate of intestinal transit (Gregory and Miller 1989). The effect is probably caused by induction of weak peristaltic rushes over long segments of intestine as is observed with similar infusions in the pig (Gregory et al. 1986). In animals with simple stomachs, these infusions release a variety of gut-active hormones, of which the most important are probably secretin and cholecystokinin (Walsh 1987). Both of these hormones inhibit abomasal motility and outflow (McLeay and Moran 1979) and reticuloruminal motility (Grovum 1981); cholecystokinin stimulates small intestinal transit and disrupts the MMC (P. C. Gregory, unpublished), and secretin increases MMC frequency (Bueno et al. 1975). Direct evidence is presently lacking for the involvement of specific hormones in these responses, but the recent production of highly specific cholecystokinin antagonists may make it possible to identify which, if any, effects of luminal stimuli are due to cholecystokinin secretion.

VII. Conclusions

Together with the papers from previous symposia, notably those of Iggo and Leek (1970), Leek and Harding (1975) and Bueno and Fioramonti (1979), this review demonstrates how we are beginning to identify the importance of some of the complex mechanisms that regulate GI-tract motility in the ruminant. In many areas our knowledge is thin: for sensory mechanisms there are few data on the sensitivity of the omasum, liver, and large intestine in ruminants, and the relationship between enteroceptors in local and projecting reflex mechanisms is unknown; for motor control there is limited detail about the functional relationship between efferent command neurons and their target organs, and almost nothing is known about intrinsic reflex mechanisms in the vagus-intact animal. The regulatory mechanisms by luminal stimuli are modified by other factors, which are not all mentioned here, such as fasting, inherent circadian rhythms, and the postprandial release of GI-tract and other hormones, all of which require further study and appropriate experimental procedures.

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