Awatif B. Al-Backer

Intestine  Involuntary structure with myogenic contraction (spontaneous rhythmic contraction) which undergo control of nervous system.  It is under the control of sympathetic & para- sympathetic innervations.  Intestine is composed of duodenum, jejunum & ileum.

SympatheticParasympathetic Neurotrans- mitter Adrenaline & noradrenaline Acetylcholine Receptors Adrenergic receptors: ( Adrenergic receptors: ( α1, β2) Cholinergic receptors ( neuronal nicotinic Nn & peripheral muscrinic receptors M3) Action Inhibitory muscle contraction Excitatory muscle contraction Parasympathetic Ach NA Neuroeffector junction ANS Sympathetic Pre-ganglionic nerve Post-ganglionic nerve Autonomic N.S Innervation in the Intestine

Awatif B. Al-Backer Enteric Receptors 1.Histaminergic receptors. 2.Serotonergic receptors. 3.Purinergic receptors.

Drugs Acting on Intestine 1- STIMULANTS: They are called spasmogenic 2- DEPRESSANTS: They are called spasmolytic Awatif B. Al-Backer

SPASMOGENIC DRUGS (Excitatory) 1- Autonomic Cholinergic Stimulant:- A- Central nicotinic neuronal (Nn) R agonist (ganglionic stimulant): * Act on Nn R present in autonomic ganglia * Ex. Small dose of nicotine ( dil. Nicotine) * MOA of dil.nicotine: Dil. Nicotine stimulates Gs protein in cell membrane → activates Na channels → rapid ↑ intracellular Na → depolarization and AP muscle contraction Awatif B. Al-Backer

ACTION POTENTIAL

Awatif B. Al-Backer B- Muscarinic receptors agonist ( cholinomimetic): * Act on muscarinic M3 receptors. * Ex.: 1- Ach & its derivatives e.g. methachloine, bethanecol, carbacol 2- Naturally occurring alkaloids e.g. Pilocarpine * MOA of Ach: Ach ++ M3R → ++ Phospholipase C → Hydrolysis of phosphatidylinositol biphosphate (PIP2) into: 1- DAG (diacylglycerol) → ↑opening of Calcium channels 2- IP3 (inositol triphosphate) → mobilization of cal. from its stores 1, 2 lead to ↑ intracellular calcium → contraction Continue

Awatif B. Al-Backer 2- Direct acting stimulant * Ex. Bacl2 * Acts directly on muscle fibers Continue

Awatif B. Al-Backer SPASMOLYTIC DRUGS 1- Autonomic adrenergic stimulants (sympathomimetic):- * Ex. adrenaline & noradrenaline * They bind to α1, β2 receptors intestinal tone & motility muscle contraction 2- Direct depressants:- 2- Direct depressants:- * Ex. Mgcl2 & papaverine

Awatif B. Al-Backer 0.1 ml 0.1 ml 0.1 ml 0.1 ml 0.1 ml Dil.nic. Ach Bacl 2 Adr. Mgcl2 Experiment N N N N N Keys: N=Normal Dil.nic=Dilute nicotine Ach= Achetylcholine Bacl2=Barium chloride Adr.=Adrenaline Mgcl2=Magnesium chloride