5-HT inhibits spontaneous contractility of isolated sheep mesenteric lymphatics via activation of 5-HT4 receptors

Spontaneous isometric contractions were measured in rings of sheep mesenteric lymphatic vessels in vitro. 5-Hydroxytryptamine (5-HT) produced a concentration-dependent decrease in spontaneous contraction frequency and force which was not antagonised by either the nonspecific 5-HT1/5-HT2 receptor antagonist methysergide (1 muM) or the 5-HT3 receptor antagonist ondansetron (1 muM). The 5-HT4 receptor agonist BIMU-8 mimicked the inhibitory effect of 5-HT4 and its effects were abolished by the 5-HT4 receptor antagonist DAU 6285 (1. muM). DAU-6285 also abolished the inhibitory effect of 5-HT and unmasked a weak excitatory response, which was mimicked by the 5-HT2 receptor agonist alpha-methyl-5-hydroxytryptamine maleate. This excitatory response was, in turn, blocked by the 5-HT3, receptor antagonist pirenperone (1 muM). The results of this study suggest that sheep mesenteric lymphatics possess both 5-HT4 receptors and 5-HT2 receptors. The inhibitory 5-HT4 receptor appeared to be the predominant subtype since the excitatory response to 5-HT could only be observed in the presence of the 5-HT4 receptor antagonist DAU 6285. (C) 2000 Academic Press.