Effects and Sites of Action of Different Agonists Drugs (Stimulant or Relaxant)on The

Isolated Rabbit Intestine

313 PHLLab # 2

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

.1STMULANTSThey are called Spasmogenic

.2DEPRESSANTSThey 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 cell membrane) This will activate Na+/K+ channel

• Na+ influx

•increase intracellular Na+

• rapid depolarization and action potential (AP)

• intestinal smooth muscle contraction.

2(Muscarinic Receptors agonist (cholinomimetic)

-Act on muscarinic M3 recptorse.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.