Characterization of 5-hydroxytryptamine receptors on isolated ovine uterine artery in late pregnancy.
5-Hydroxytryptamine (5-HT) and 2,5-dimethoxy-4-methyl-amphetamine (DOM) are potent agonists on isolated ovine uterine arteries in late pregnancy. Similar pA2 values (8.56 and 8.33, respectively) of ketanserin, tested against 5-HT and DOM, indicate that responses produced by both agonists are mediated by the 5-HT2 receptor. The contractions produced by 8-OH-DPAT and 2-methyl-5-HT were also blocked by ketanserin (10(-8) M) with the dissociation constants (KB) being 2.49 and 2.88 nM, respectively. This provides evidence that these agonists are activating 5-HT2 receptors in the ovine uterine artery. DOM was more potent than 5-HT, but had a similar efficacy to that of 5-HT. The greater affinity of DOM may explain its greater potency. The dissociation constants (KA) of 5-HT and DOM acting on 5-HT receptors were determined by analysis of concentration-response data before and after fractional inactivation of receptors with dibenamine. The mean KA values for 5-HT and DOM were 3.7 +/- 0.7 x 10(-7) and 1.8 +/- 0.3 x 10(-7) M, respectively. Assessment of receptor occupancy vs. functional response demonstrated little or no receptor reserve in this tissue. Several other 5-HT receptor agonists caused contractions but were much less potent than 5-HT. The order of potency of these agonists was determined to be DOM greater than 5-HT greater than or equal to alpha-methyl-5-HT much greater than 8-hydroxy-dipropylaminotetralin (8-OH-DPAT) greater than 2-methyl-5-HT greater than 1-(3-chlorophenyl) piperazine (mCPP) greater than m-trifluoromethyl-phenylpiperazine (TFMPP).(ABSTRACT TRUNCATED AT 250 WORDS)
Zhang
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Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine, Iowa State University, Ames.
Dyer
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DC
D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine / Q000494:pharmacology*; D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D003983:Dibenzylchlorethamine / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D011247:Pregnancy; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D012756:Sheep; D014590:Uterine Contraction / Q000187:drug effects
D000662:Amphetamines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine; D012701:Serotonin; D003983:Dibenzylchlorethamine