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: 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 nervous system(sympathetic and parasympathetic).

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 .

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

Stimulant Drugs (Spasmogenic) A- Autonomic cholinergic stimulants , act on: 1-Nicotinic Neuronal receptor: e.g. Nicotine (small doses)= Diluted Nicotine Mechanism of Action: Diluted Nicotine activates Nn receptors in the cell membrane. This will activate Na+/K+ channel  Na+ influx increase intracellular Na+  rapid depolarization  intestinal smooth muscle contraction .

2)Muscarinic Receptors (M3 subtypes): e.g. Cholinomimetic 1-Acetylcholine or its derivative : e.g. .Methacholine, Bethanecol, Carbachol. 2- Naturally occurring alkaloid : e.g. Pilocarpine.

Mechanism of Action : 1. Acetylcholine binds with M3 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 : e.g. Barium Chloride Mechanism of Action: BaCl2 stimulates the muscle fiber  increase muscle contraction.

Inhibitory drugs (Spasmolytics) A-Autonomic adrenergic stimulants: 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 .