1. 313 PHL
Lab # 2
Effects and Sites of Action of Different Agonists Drugs (Stimulant or Relaxant)on The Isolated Rabbit Intestine

2. The nervous control of 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).

4. The intestine innervated by ANS :
Parasympathetic
Acetylcholine (Ach) .
Cholinergic:
Central: Nicotinic (Nn) .
and peripheral: muscarinic (M3)
excitatory (↑contraction) contraction
Sympathetic
Transmitter: noradrenalin mainly, Adrenaline .
Receptors present in
(intestine): Adrenergic: α1,B2
Action:
inhibitory (↓contraction) relaxation .

5. Types of receptors present in the intestine:
Adrenergic.
Cholinergic.
Histaminergic.
Purinergic.
Serotinergic.

6. Drug Acting on Intestine
STMULANTS
They are called Spasmogenic
DEPRESSANTS
They are called Spasmolytic

7. 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

8. Mechanism of Action: Diluted Nicotine
Dil.Nicotine stimulates gated ion channels receptors in the cell membrance (activates Nn receptors in the cell membrane) This will activate Na+/K+ channel
 Na+ influx
increase intracellular Na+
 rapid depolarization and action potential (AP)
 intestinal smooth muscle contraction .

9. 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.

10. 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.

11. 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.

12. 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.

13. 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 .

14. Inhibitory drugs (Spasmolytic)
B-Direct Inhibitory Drugs :
e.g. Mgcl2
Papaverine
Mechanism of Action : Mgcl2 inhibits the contraction of muscle fiber  muscle relaxation .