Pharmacological characterization of the 5‐HT receptor‐mediated contraction in the mouse isolated ileum

The pharmacological characterization of a 5‐HT receptor‐mediated contractile response in the mouse isolated ileum is described. In the presence of methysergide (1 μ M ), 5‐hydroxytryptamine (5‐HT, 0.3–100 μ M ) produced phasic concentration‐dependent contractions of segments of the mouse isolated ileum with a pEC 50 value of 5.47±0.09. The 5‐HT 3 receptor selective agonists m‐chlorophenylbiguanide (0.3–100 μ M , pEC 50 5.81±0.04), 1‐phenylbiguanide (3–100 μ M , pEC 50 5.05±0.06) and 2‐methyl‐5‐HT (3–100 μ M , pEC 50 5.00±0.07) acted as full agonists to induce contractile responses. 5‐methoxytryptamine (0.1–100 μ M ), RS 67506 (0.1–100 μ M ) and α‐methyl‐5‐HT (0.1–100 μ M ) failed to mimic the 5‐HT responses. The contractile response to 5‐HT was not antagonized by either 5‐HT 2 receptor antagonists ritanserin (0.1 μ M ) or ketanserin (1 μ M ) nor the 5‐HT 4 receptor antagonist SB 204070 (0.1 μ M ). The 5‐HT 3 receptor selective antagonists granisetron (0.3–1 n M ), tropisetron (1–10 n M ), ondansetron (10 n M –1 μ M ) and MDL 72222 (10 n M –1 μ M ) caused rightward displacement of the concentration‐response curves to 5‐HT. The lower concentrations of the antagonists caused approximate parallel rightward shifts of the concentration‐response curves to 5‐HT with apparent pK B values for granisetron (9.70±0.39), tropisetron (9.18±0.20), ondansetron (8.84±0.24) and MDL 72222 (8.65±0.35). But higher concentrations of antagonists resulted in a progressive reduction in the maximum responses. The contractile response to 5‐HT was abolished by tetrodotoxin (0.3 μ M ); atropine (0.1 and 1 μ M ) decreased the maximum response of the 5‐HT concentration‐response curve by approximately 65%. It is concluded that a neuronally located 5‐HT 3 receptor mediates a contractile response to 5‐HT in the mouse ileum. The 5‐HT 3 receptor in the mouse ileum has a different pharmacological profile to that reported for the guinea‐pig ileum.British Journal of Pharmacology (2000) 131 , 1716–1722; doi: 10.1038/sj.bjp.0703747