Pharmacological characterization of the 5-HT receptor-mediated contractionin the mouse isolated ileum

1 The pharmacological characterization of a 5-HT receptor-mediated contract ile response in the mouse isolated ileum is described. 2 In the presence of methysergide (1 muM), 5-hydroxytryptamine (5-HT, 0.3-1 00 muM) produced phasic concentration-dependent contractions of segments of the mouse isolated ileum with a pEC(50) value of 5.47+/-0.09. 3 The 5-HT3 receptor selective agonists m-chlorophenylbiguanide (0.3-100 mu M, pEC(50) 5.81+/-0.04), 1-phenylbiguanide (3-100 muM, pEC(50) 5.05+/-0.06) and 2-methyl-5-HT (3-100 muM, pEC(50) 5.00+/-0.07) acted as full agonists to induce contractile responses. 5-methoxytryptamine (0.1-100 muM), RS 6750 6 (0.1-100 muM) and alpha -methyl-5-HT (0.1-100 muM) failed to mimic the 5- HT responses. 4 The contractile response to 5-HT was not antagonized by either 5-HT2 rece ptor antagonists ritanserin (0.1 muM) or ketanserin (1 muM) nor the 5-HT4 r eceptor antagonist SE 204070 (0.1 muM). 5 The 5-HT3 receptor selective antagonists granisetron (0.3-1 nM), tropiset ron (1-10 nM), ondansetron (10 nM-1 muM) and MDL 72222 (10 nM-1 muM) caused rightward displacement of the concentration-response curves to 5-HT. The l ower concentrations of the antagonists caused approximate parallel rightwar d shifts of the concentration-response curves to 5-HT with apparent pK(B) v alues 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 an tagonists resulted in a progressive reduction in the maximum responses. 6 The contractile response to 5-HT was abolished by tetrodotoxin (0.3 muM); atropine (0.1 and 1 muM) decreased the maximum response of the 5-HT concen tration-response curve by approximately 65%. 7 It is concluded that a neuronally located 5-HT3 receptor mediates a contr actile response to 5-HT in the mouse ileum. The 5-HT3 receptor in the mouse ileum has a different pharmacological profile to that reported for the gui nea-pig ileum.