313PHL Lab #4 Identification of effect and site of action of an unknown drug using isolated guinea-pig ileum.

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313PHL Lab #4 Identification of effect and site of action of an unknown drug using isolated guinea-pig ileum

Guinea pig ileum is a smooth muscle receive dual nerve supply from autonomic nervous system (sympathetic and parasympathetic) . Parasympathetic tone is dominant in ileum which Ach cause contraction by stimulating M3-R .

Why Guinea pig ileum is used? No myogenic contraction so any drug induce contraction can be seen. Very sensitive to histamine unlike the rabbit due to the presence of histaminase enzyme.

Types of receptors present in guinea-pig ileum Cholinergic receptors . Serotonergic or tryptaminergic receptors (5-HT1→5-HT7) . Histaminergic receptors . Adrenergic receptors .

Types of receptors in guinea-pig ileum: 1- Cholinergic receptors: Receptor Agonist Antagonist nicotinic neuronal receptor (Nn- R) Dil. Nicotine Conc. Nicotine muscarinic receptor(M3 -R) Ach Atropine

Types of receptors in guinea-pig ileum: 2-Serotonergic or tryptaminergic (5-HT )receptors : Serotonin = 5-HT(5-hydroxytryptamine) . 5-HT2A receptor found in smooth muscle and bronchi . Receptor Agonist Antagonist 5-HT2A serotonin -Methysergide & ketanserin (selective) . -cyproheptadine (non selective block both H &5-HT receptors) .

Types of receptors in guinea-pig ileum: 3- Histaminergic receptors: Histamine is an autacoids naturally occurring in the body . Receptor distribution Action Agonist Antagonist H1 Smooth muscles contraction Histamine Mepyramine cyproheptadine H2 Gastric mucosa Gastric acid secretion Cimetidine Ranitidine H3 Presynaptic Decrease release of Histamine Thioperamide

Types of receptors in guinea-pig ileum: 4- Adrenergic receptors: Receptor Agonist Antagonist α1 Adrenaline phentolamine ß 2 -

Types of drugs act on guinea-pig ileum : Spasmogens: 1- Cholinergic stimulants , e.g. Ach . MOA : 2- Histaminergic stimulants, e.g. Histamine . MOA: histamine act on H1 R which coupled with Gαq → stimulate PLC → Hydrolysis of (PIP2) into: 1- DAG → ↑opening of Ca+2 channels 2- IP3 → mobilization of Ca+2 from its stores 1&2 → ↑ intracellular Ca+2 → Contraction .

Spasmogens: 3- Serotonergic stimulants . e.g. Serotonin. 4- Direct acting stimulants (spasmogens) . e.g. Barium chloride, Calcium chloride .

Spasmolytics : 1- Direct acting Spasmolytics . e.g. Mgcl2 Papaverine

Experiment Identification of effect and site of action of an unknown drug using isolated guinea-pig ileum   Blocker + Agonist Unknown Unknown Agonist

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