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Characterization of serotonergic receptors mediating contraction of ovine umbilical artery

LB Zhang and DC Dyer

Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine, Iowa State University, Ames, Iowa.

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.

Volume 255, Issue 1, pp. 233-239, 10/01/1990
Copyright © 1990 by American Society for Pharmacology and Experimental Therapeutics




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Copyright © 1990 by the American Society for Pharmacology and Experimental Therapeutics.