Effect of Certain Agonists & Antagonists on Isolated Guinea-pig Ileum

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Effect of Certain Agonists & Antagonists on Isolated Guinea-pig Ileum Lab #4

Objectives Discuss the types of receptor present in guinea-pig ileum Explain the action of agonists & their specific antagonists Discuss the reasons for using guinea-pig ileum Explain of effect of different drugs on isolated guinea-pig ileum curve

Types of receptors in GPI 1- Cholinergic receptors 2- Serotonergic or tryptaminergic receptors (5-HT1→5-HT7) 3- Histaminergic receptors

Cholinergic receptors 1- NN R Agonist: Dil. Nicotine Antagonist: Conc. Nicotine 2- M3 R Agonist: Ach Antagonist: Atropine

Serotonergic or tryptaminergic receptors Serotonin = 5-HT(5-hydroxytryptamine) 5-HT receptors in GPI: 5-HT2A Agonist: serotonin Antagonist: ketanserin methysergide cyproheptadine (blocks 5-HT2A & H1)

Histaminergic receptors R subtype Distribution Action Agonist Antagonist H1 Smooth muscles contraction Histamine Mepyramine cyproheptadine H2 Gastric mucosa Gastric acid secretion Cimetidine Ranitidine H3 Presynaptic Autoregulation of H release Thioperamide N.B. Histamine acts by stimulating Gs protein → ↑ cAMP → ↑ [Calcium]ic → contraction

e.g. Barium chloride e.g. Papaverine Direct acting drugs Direct spasmogen e.g. Barium chloride Direct spasmolytic e.g. Papaverine

Advantages of GPI No myogenic contraction More sensitive to histamine

Experiment N Key: Hist.=histamine AH= antihistamine 5-HT=serotonin W N 0.1ml Bacl2 0.1ml 5-HT Ach 0.1ml Hist. 0.1ml W+N W+N Ach 0.1ml AH 0.2 ml Hist. 0.1ml Bacl2 0.1ml Atropine 0.1ml 5-HT 0.1ml Papaverine 0.1ml Key: Hist.=histamine AH= antihistamine 5-HT=serotonin

Experiment Identification of site of action of an unknown drug using isolated guinea-pig ileum N W N W+N W+N Ach 0.1ml Hist. 0.1ml Unk. Unk. Ach 0.1ml Hist. 0.1ml Atropine 0.1ml AH 0.2 ml Key: Ach= acetylcholine Hist.=histamine AH= antihistamine Unk.= unknown