5‐HT receptor types in the rat ileum longitudinal muscle: focus on 5‐HT2 receptors mediating contraction

The 5‐hydroxytryptamine (5‐HT) receptor(s) that mediate(s) contraction of the rat ileum longitudinal muscle was studied. 5‐HT and α‐methyl‐5‐HT equipotently induced contractions, whereas 5‐methoxytryptamine and 2‐methyl‐5‐HT (partial agonist) were less potent; this rank order of potency suggests involvement of a 5‐HT2 receptor. Neither tetrodotoxin nor atropine affected the contraction to 5‐HT, suggesting a smooth muscle localization of these 5‐HT2 receptors. The presence of either a selective 5‐HT2B (SB 204741), 5‐HT3 (granisetron) or 5‐HT4 (SB 204070) antagonist, slightly affected the contractions to 5‐HT. Thus, they were also included in the organ bath solution in all subsequent experiments in order to pharmacologically isolate the main contractile component. Using (if possible) 5‐HT2A receptor‐selective concentrations, ketanserin, ritanserin, metergoline, spiperone, mianserin, methiothepin, mesulergine, methysergide and cisapride all inhibited the contractions to 5‐HT, causing a depression of the curve to 5‐HT (i.e. surmountable antagonism was not observed with any of the above agents). Comparison of the affinities of these compounds for the various 5‐HT2 receptor subtypes revealed that the receptor involved in the contractions to 5‐HT most closely resembles the 5‐HT2A receptor. However, cinanserin at a concentration expected to inhibit 5‐HT2A receptor‐mediated effects, failed to affect the contractions to 5‐HT. It is thus concluded that on the longitudinal smooth muscle of the rat ileum, at least a part of the contraction to 5‐HT is mediated by 5‐HT receptors resembling the 5‐HT2A receptor subtype.