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313 PHL
Lab # 2
Effects and Sites of Action of Different Agonists
Drugs (Stimulant or Relaxant)on The
Isolated Rabbit Intestine
The nervous control of intestine:
Intestine :
Is composed of(duodenum,jejunum,ileum) .
It is a Smooth muscle & has myogenic contraction
(i.e. spontaneous rhythmic contraction).
N.B this rhythmicity due to its pendular movement.
Is involuntary muscle undergoes the control of
autonomic nervous system(sympathetic and
parasympathetic).
The intestine innervated by ANS :
Sympathetic
Transmitter: noradrenalin
mainly, Adrenaline .
Receptors present in
(intestine): Adrenergic: α1,B2
Action:
inhibitory (↓contraction)
relaxation .
Parasympathetic
Acetylcholine (Ach) .
Cholinergic:
Central: Nicotinic (Nn) .
and peripheral: muscarinic
(M3)
excitatory
(↑contraction)
contraction
Types of receptors present in the intestine:
 Adrenergic.
 Cholinergic.
 Histaminergic.
 Purinergic.
 Serotinergic.
Drug Acting on Intestine
STMULANTS .1
They are called Spasmogenic
DEPRESSANTS .2
They are called Spasmolytic
Stimulant Drugs (Spasmogenic)
A- Autonomic cholinergic stimulants , act on:
1- Central Nicotinic Neuronal receptor agonist (Nn) R
(ganglionic stimulant):
- Act Nn R present in autonomic ganglia
e.g. Nicotine (small doses)= Diluted Nicotine
Mechanism of Action:
Diluted Nicotine •
Dil.Nicotine stimulates gated ion channels receptors in
the cell membrance (activates Nn receptors in the
membrane) This will activate Na+/K+ channel cell
 Na+ influx •
increase intracellular Na+ •
 rapid depolarization and action potential (AP) •
 intestinal smooth muscle contraction . •
2)Muscarinic Receptors agonist (cholinomimetic)
-Act on muscarinic M3 recptors
e.g. Cholinomimetic
Ex.:
1-Acetylcholine(Ach) and its derivative : e.g. .Methacholine,
Bethanecol,
Carbachol.
2- Naturally occurring alkaloid : e.g. Pilocarpine.
Mechanism of Action :
1. Acetylcholine binds with M3R receptors  activation of PLC
( phospholipase C) .
2. PLC hydrolyzes PIP2(phosphotidyl inositol biphosphate) into
DAG and IP3 .
DAG=diacylglycerol.
IP3= inositol triphosphate.
3. DAG activates Ca+ + channel  increase intracellular Ca+ +.
4.IP3 increase Ca+ + release from intracellular stores.
3,4  increase intracellular Ca+ +  intestinal smooth muscle
contraction.
Stimulant Drugs (Spasmogenic)
B-Direct smooth muscle stimulants (Direct acting
stimulant) :
e.g. Barium Chloride (Bacl2)
Mechanism of Action:
BaCl2 stimulates act directly on the muscle fiber  increase
muscle contraction.
Inhibitory drugs (Spasmolytics)
A-Autonomic adrenergic stimulants
(sympathomimetic):
e.g. Adrenaline, Noradrenaline
Mechanism of Action:
Adrenaline will stimulate α1 and ß 2 receptors in the intestinal
smooth muscle
 inhibits tone and motility
 decrease intestinal contraction .
Inhibitory drugs (Spasmolytic)
B-Direct Inhibitory Drugs :
e.g. Mgcl2
Papaverine
Mechanism of Action :
Mgcl2 inhibits the contraction of muscle fiber  muscle
relaxation .