PRESENTED BY, SANTHOSH.C M 1st M.Pharm Dept.

of Pharmacology GCP

also called as parasympathetic nervous system. origin: cranio sacral nerves. NT: Ach Ganglia is close to organ

Preganglionic neurons

Long Synapse with postganglionic neurons at or near organ Release acetylcholine (ACH) to activate nicotinic receptors on postganglionic neurons

Postganglionic neurons

Short Synapse on the target organ Release acetylcholine (ACH) to activate muscarinic receptors on the target organ

Synthesis of Acetylcholine

Parasympathetic Ganglionic Synapse

Acetylcholinesterase

Na+

Action Potential

aba

ACH

Nicotinic Receptor

Na+
Preganglionic neuron

Postganglionic neuron

Parasympathetic Organ Synapse

Acetylcholinesterase

Na+

Effector Organ

K+

G
Action Potential

ACH
Muscarinic Receptor

Postganglionic neuron

Cholinergic Receptors

Nicotinic

Muscarinic

Nn

Nm

CNS

Cholinergic Receptors

Nicotinic

Muscarinic

M1

M3

M5

M2

M4

*They are ligand gated cation channels (Ionotropic receptors) (Nm) *Fast acting receptors *It is assembled from 4 diff subunits (,,,) *Receptors pentameric structure possess 2 Ach binding subunits
a

d
a

Types

Muscle type(Nm)

Ganglion type(Nn)

CNS type

Location

NMJ

Autonomic ganglia(post synaptic )

Excitatory (influx of Na+)

Pre &post synaptic nerves

Incresed Ca2+permiabil ity

Response

Excitatory (influx of Na+)

Agonists

Ach ,nicotine, Carbachol, Succinylcholine PTMA Tubocurarine, Panocurarine,

Ach,nicotine, Carbachol, DMPP

DMPP

Antagonists

Hexamethonium Mecamylamine, Trimathaphan

Methylaconite

Muscarinic receptors: all G-protein linked

M1: Gq *Gastric secretion in parietal cells and depolarization of autonomic and CNS neurons M2: Gi * Negative inotropic and chronotropic effect on the heart * it also acts as auto receptor. M3: Gq * Stimulates smooth muscle contraction; sweat, bronchial and salivary secretions;

Muscarinic receptors
M1 (neural) Locations Ganglia M2 (cardiac) Heart :Atria CNS, M3(glands/ smooth muscle) Exocrine glands, eye, airways, IP3 , stimulation, Ca2+ all secretion bethanechol M4 M5 CNS Salivary glands , ciliary muscles IP3 ,DAG Exitation

Cellular response

IP3, DAG, Depolarisation (exitation) CNS exitation Gastric secretion Ach, Oxotremorine

cAMP , Hyperpolaris ation (Inhibition) FOC ROC Methacholine

cAMP, Inhibition

Functional response Agonists

Not known

Not known

Antagonist Atropine, s PIRENZEPINE

Gallamine, ipratropium

Atropine, Atropine,i Methoctram pratropiu ine m

Atropine, ipratropiu m

NH3

(+) Phospho-

Gq

lipase C
PIP2

COOH

IP3 Increase Ca2+

Diacylglycerol Activate Protein Kinase C

Response

NH 3

(-)

Adenylate Cyclase

GI

K+

(+) ATP COOH

X
cAMP Reduce cAMP-Dependent Protein Kinase Activity

Response

Muscarinic Autonomic Effects of Acetylcholine

Eye (iris sphincter muscle)

Eye (ciliary muscle) SA node Atrium Arteriole Bronchial muscle Bronchial secretion GIT (motility) GIT (secretion) GIT (sphincters) Urinary bladder (wall) Urinary bladder (sphincter) Penis Sweat glands Salivary glands Lacrimal glands

Contraction (miosis)
Contraction (for near vision) Bradycardia (slow heart rate) Reduced contractility Dilatation Muscle Contraction Increase Increase Increase Relaxation Contraction Relaxation Erection (but not ejaculation) Secretion (sympathetic cholinergic!) Secretion Secretion

Difference b/w adrenergic and cholinergic effects

Effector Organ

Adrenergic Response
Increase Increase

Receptor
b1 b1

Cholinergic Response
Decrease Decrease

Receptor
M2 M2

Heart
Rate of Contraction Force of Contraction

Effector Organ
Arteries (most) Veins Skeletal Muscle Endothelium

Adrenergic Response
Vasoconstriction Vasoconstriction Vasodilation ----------

Cholinergic Receptor Response

a1 a2 b2 ----------------------------Release EDRF

Receptor
---M3

Effector Organ Lung

Bronchiolar smooth muscle

Adrenergic Response
Bronchodilation

Cholinergic Receptor Response

b2

Receptor
M3

Bronchoconstriction

Effector Organ

Adrenergic Response

Cholinergic Receptor Response

b2 a1 a1 b2 a1 a1

Receptor

Genitourinary, smooth muscle

Bladder wall Ureter Sphincter Uterus (pregnant) Penis/vas deferens Relaxation Contraction Contraction Relaxation Contraction Ejaculation Contraction Relaxation Relaxation Variable M3 M3 M3 M3 M3

Erection

Effector Organ

Adrenergic Response

Cholinergic Receptor Response

a1 a2 , b 2

Receptor

Gastrointestinal Tract
Salivary Glands Smooth Muscle: Walls Sphincters Secretion Increase secretion Relaxation Contraction ---------Increase secretion Contraction Relaxation Increase secretion M3 M3 M3 M3

a1
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