Abstract

Effects of 5-hydroxytryptamine (5-HT) agonists were investigated in the bovine isolated mesenteric lymphatics, and then the 5-HT receptor subtypes in the responses were pharmacologically classified by use of several 5-HT antagonists. Addition of 5-HT and that of alpha-methyl-5-hydroxytryptamine (alpha-methyl-5-HT) both produced concentration-dependent contractions in the presence of 3 x 10(-6) M [(1 alpha H, 5 alpha H)-8-methyl-8-azabicyclo(3.2.1)oct-3 alpha-yl]1H-indole-3-carboxylate hydrochloride, whereas 5-carboxamidotryptamine (5-CT) and 2-methyl-5-hydroxytryptamine (2-methyl-5-HT) caused no, or only slight, contraction in the lymphatics. Pretreatment with ketanserin caused a significant shift to the right in the concentration-response curve for 5-HT or alpha-methyl-5-hydroxytryptamine. Schild plot analyses showed that the pA2 values for ketanserin against 5-HT and alpha-methyl-5-hydroxytryptamine were 8.75 and 8.68, respectively. In contrast, 5-CT, 5-HT and metoclopramide caused concentration-dependent relaxations in the presence of 10(-6) M ketanserin in the lymph vessels after contraction with prostaglandin F2 alpha. 2-Methyl-5-HT up to 10(-4) M did not produce any relaxation. High concentrations of [(1 alpha H, 5 alpha H)-8-methyl-8-azabicyclo(3.2.1)oct-3 alpha-y1]1H-indole-3-carboxylate hydrochloride induced a significant inhibition of the 5-CT- and 5-HT-induced relaxation, but methiothepin and methysergide up to 10(-6) M and mechanical rubbing of the endothelium had no significant effect on the relaxation.(ABSTRACT TRUNCATED AT 250 WORDS)