Investigation into the 5-hydroxytryptamine-induced relaxation of the circular smooth muscle of guinea-pig stomach fundus

Abstract

The 5-HT receptor that mediates relaxation of circular muscle strips of the guinea-pig stomach fundus under resting tone was investigated. Concentration-dependent relaxation was obtained in the presence of atropine (0.2 μM) with 5-hydroxytryptamine (5-HT) (apparent mean pEC 50 value, 5.27), 5-carboxamidotryptamine (7.35),-methoxytryptamine (4.98) and 5-methyltryptamine (4.58). 1-(m-Trifluoromethyl-phenyl)piperazine and 8-hydroxy-2-(di-n-propylamino)tetralin acted as partial agonists while 2-methyl-5-hydroxytryptamine, α-methyl-5-hydroxytryptamine, sumatriptan, metoclopramide and cisapride had little or no effect on the guinea-pig stomach fundus. The concentration-response curve for 5-HT was not affected by tetrodotoxin (0.3 μM), guanethidine (5 μM) or indomethacin (2 μM), suggesting that the relaxation is non-neuronal in origin and is independent of the release of catecholamines or prostanoids. The non-selective 5-HT receptor antagonist, metitepine (0.03–0.1 μM), the 5-HT IC/5-HT 2 receptor antagonists, mianserin (0.3–1 μM), pizotifen (0.3–1 μM), ketanserin (3–10 μM), and the 5-HT 1A/5-HT 2 receptor antagonist, spiperone (3 μM), shifted the concentration-response curves for 5-HT to the right. A 5-HT 3 receptor antagonist, ICS205-930 (1 μM), propranolol (1 μM) and phentolamine (1 μM) failed to block the 5-HT-induced relaxation. In conclusion, the results found with agonists and antagonists are compatible with the view that a 5-HT 1-like receptor is involved in 5-HT-induced direct relaxation of circular muscle of guinea-pig stomach fundus.