Smooth muscle 5‐HT 2A receptors mediating contraction of porcine isolated proximal stomach strips

The aim of this study was to characterize the 5‐HT receptors involved in the 5‐HT‐induced contraction of longitudinal muscle (LM) strips of porcine proximal stomach. This was done in a classical organ bath set‐up for isotonic measurement. The concentration‐contraction curve to 5‐HT was not modified by 5‐HT 3 and 5‐HT 4 receptor antagonism. Methysergide, ketanserin and mesulergine antagonized the curve to 5‐HT. Concomitantly, increasing concentrations of ketanserin and mesulergine progressively revealed a biphasic nature of the 5‐HT curve. Ketanserin antagonized the low‐affinity receptor while it did not modify the high‐affinity receptor. Tetrodotoxin did not influence the concentration‐contraction curve to 5‐HT neither in the absence nor presence of ketanserin, indicating that nerves are not involved. Ketanserin competitively antagonized the monophasic concentration‐response curve to α‐Methyl‐5‐HT, yielding a Schild slope that was not significantly different from unity. After constraining the Schild slope to unity, a pK B estimate of 8.23±0.90 was obtained. This affinity estimate of ketanserin closely approximates previously reported affinities at 5‐HT 2A receptors. In the presence of ketanserin (0.1 μ M ; exposing the high‐affinity receptor), a wide range of 5‐HT receptor antagonists covering all 5‐HT receptors known, was tested. Only methysergide and ritanserin inhibited the response to 5‐HT, thus expressing affinity for the high‐affinity receptor. This did not reveal the identity of the receptor involved. It can be concluded that 5‐HT induces pig proximal stomach (LM) contraction via 5‐HT 2A receptors located on smooth muscle. A ketanserin‐insensitive phase of contractions could not be characterized between the actually known classes of 5‐HT receptors with the pharmacological tools that were used.British Journal of Pharmacology (2002) 137 , 1217–1224. doi: 10.1038/sj.bjp.0704992