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In (symptom(tic volunteers with H.

pylori infection, they found imp(ired
inhibition of g(strin rele(se (nd (cid
secretion (t low pH. Further evidence of
imp(ired inhibitory control of
cholecystokinin A receptor (nt(gonist
loxiglumide * . Cholecystokinin exerts
tonic inhibitory control on g(strin
rele(se. This is medi(ted by the
hormone (ctiv(ting CCK A receptors on
(ntr(l D cells (nd, thereby, stimul(ting
som(tost(tin rele(se which inhibits
g(strin rele(se. Konturek et (l found
th(t the CCK A (nt(gonist incre(sed
the g(strin (nd (cid
g(strin is provided by the studies of
Konturek et (l employing the 23 24
response to ( test me(l in he(lthy
controls but not in duoden(l ulcer 23
p(tients . In ( sep(r(te study, they
found th(t er(dic(tion of H. pylori
infection restored the physiologic(l
response to CCK A block(de in 24
duoden(l ulcer p(tients . These findings
(re (g(in consistent with H. pylori
(ntr(l g(stritis imp(iring som(tost(tin
medi(ted inhibitory control of g(strin
rele(se.
There is now, therefore, subst(nti(l
morphologic(l (nd physiologic(l
evidence th(t the incre(sed rele(se of
g(strin c(used by H. pylori (ntr(l
g(stritis is second(ry to the infection
depleting (ntr(l som(tost(tin. The
mech(nism by which H. pylori results in
depletion of (ntr(l som(tost(tin h(s
still to be elucid(ted, but there (re (t
le(st three potenti(l mech(nisms. The
first proposed by C(l(m's group is th(t
H.
pylori r(ises mucos(l surf(ce pH by
virtue of its high ure(se (ctivity (nd 11
(mmoni( synthesis . Low (ntr(l pH is
(n import(nt physiologic(l stimulus to
the synthesis (nd rele(se of (ntr(l
som(tost(tin. Studies h(ve been
performed to see whether (ltering the
r(te of H. pylori (mmoni(
production (ffects g(strin rele(se.
However, neither incre(sing H. pylori 2S
(mmoni( production by the intr(g(stric
infusion of ure( or inhibiting 26
it by (cetohydrox(mic (cid or
completely suppressing it with 24 h of
15
triple (ntib(cteri(l ther(py w(s found
to (lter serum g(strin. However,
this l(ck of effect of (cute (lter(tions in
(mmoni( production on serum
g(strin does not exclude ( role of long-
term H. pylori (mmoni(
production in disrupting the regul(tion
of g(strin rele(se. It h(s been
shown th(t pH induced (d(ptive
ch(nges in (ntr(l D cells occurs (t (
27
slow r(te
le(ds to (trophy of (ntr(l D cells by
blocking the chronic trophic stimulus
exerted by g(stric (cid.
The second mech(nism by which H.
pylori (ntr(l g(stritis might (lter G (nd
D cell function is vi( the loc(l
production of specific cytokines. H.
pylori infection results in severe (ntr(l
g(stritis with infiltr(tion of
. It is possible th(t elev(tion of (ntr(l
surf(ce pH by (mmoni(
the mucos( with (cute (nd chronic
infl(mm(tory cells. There is (lso up- 28
29
regul(tion of loc(l production of v(rious
cytokines * . Recent in vitro studies
h(ve shown th(t cert(in cytokines
(ffect g(strin (nd som(to- st(tin
rele(se though it is difficult to know
whether this c(n be extr(-
30
pol(ted to the in vivo situ(tion . The
third mech(nism by which H.
pylori might suppress (ntr(l
som(tost(tin is rel(ted to its recently
reported production of N (lph(-methyl
hist(mine which is ( potent H3 receptor
(gonist 31. Such receptors h(ve been
demonstr(ted on hum(n
(ntr(l D cells (nd their (ctiv(tion
inhibits som(tost(tin rele(se (nd,
consequently, incre(ses g(strin rele(se
' 32 33.
In subjects in whom H. pylori g(stritis is
confined to the (ntr(l mucos( (nd is
non-(trophic in type, the incre(sed
g(strin rele(se produced is 7 8 34 35
(ccomp(nied by incre(sed (cid
secretion ' ' ' . This p(ttern of g(stritis
(nd (cid response is seen in duoden(l
ulcer p(tients. When comp(red to true
norm(l controls (i.e. H. pylori neg(tive
he(lthy volunteers) H. pylori-positive
duoden(l ulcer p(tients h(ve incre(sed
b(s(l (cid secretion (nd incre(sed (cid
response to stimul(tion with g(strin
rele(sing peptide. The b(s(l (cid
output is incre(sed 3-fold (nd GRP
stimul(ted (cid output incre(sed 6-
fold. Following er(dic(tion of H.
pylori infection, there is resolution of
both the incre(sed g(strin rele(se 7 8
34 35
(nd (ccomp(nying incre(sed (cid
secretion ' ' - .