Characterization of serotonergic receptors mediating contraction of ovine umbilical artery.
Responses to serotonergic agonists were studied in isolated umbilical arteries obtained from fetal lambs within 2 weeks of term. The order of potency of the agonists was determined to be 2,5-dimethoxy-4-methyl-amphetamine (DOM) greater than 5-hydroxytryptamine (5-HT) greater than alpha-methyl-5-HT greater than 1-(3-chlorophenyl) piperazine = m-trifluoromethyl-phenylpiperazine greater than 8-hydroxy-dipropylaminotetralin greater than 2-methyl-5-HT greater than 1-(2-methoxyphenyl) piperazine. Variations in the sensitivity and potency of the agonists results primarily from the variation in the affinity for the 5-HT2 receptor and less so in the efficacy, alpha-Methyl-5-HT was a full agonist compared to 5-HT. The others were partial agonists. The mean KA values for 5-HT and DOM were 4.71 +/- 0.62 x 10(-7) and 0.36 +/- 0.04 x 10(-7) M, respectively. Contractions to 5-HT and DOM were antagonized by ketanserin with pA2 values being 9.4 and 9.1, respectively, suggesting that they act on the same receptor and that their responses are mediated by 5-HT2 receptors. Contractile responses to 8-hydroxy-dipropylaminotetralin, 2-methyl-5-HT and the phenylpiperazines [m-trifluoromethyl-phenylpiperazine and 1-(3-chlorophenyl) piperazine] were also blocked by ketanserin (10(-8) M), indicating that contractions produced by these agonists were mediated by 5-HT2 receptors. No antagonism by MDL 72222 (3-tropanyl-3,5-dichlorobenzoate) of responses to 5-HT indicates that 5-HT3 receptors are not present in this tissue.
Zhang
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LB
Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine, Iowa State University, Ames, Iowa.
Dyer
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DC
D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine / Q000494:pharmacology; D000818:Animals; D005260:Female; D066298:In Vitro Techniques; D007650:Ketanserin / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011247:Pregnancy; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology; D012756:Sheep; D014469:Umbilical Arteries / Q000187:drug effects / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects*
D010879:Piperazines; D011985:Receptors, Serotonin; D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine; C018406:1-(3-trifluoromethylphenyl)piperazine; D012701:Serotonin; D007650:Ketanserin; C015068:1-(3-chlorophenyl)piperazine