Canine basilar artery contractions mediated by 5-hydroxytryptamine1A receptors.
A series of 11 agents was analyzed at both 5-hydroxytryptamine1A (5-HT1A) sites labeled by [3H]-8-hydroxy-2-(N,N-dipropylamino)tetralin and total 5-HT1 binding sites labeled by [3H]-5-HT in rat brain membranes. Three distinct patterns of relative inhibition were noted. First, drugs such as 8-hydroxy-2-(N,N-dipropylamino)tetralin n-(3-acetylaminophenyl)piperazine hydrochloride, 2-[4-[4-(2-pyrimidinyl)-1-piperazinyl]-1,2-benziso-thiazol-3 -(2H)one-1,1-dioxidehydrochloride] and buspirone display 1.0 to 15 nM potency for the 5-HT1A subpopulation of 5-HT1 binding sites but are more than two orders of magnitude less potent at total 5-HT1 sites. Secondly, 5-methoxy-N,N-dimethyltryptamine and methysergide are approximately one order of magnitude more potent at 5-HT1A than total 5-HT1 sites. In the third group, 5-HT, d-lysergic acid diethylamide, 1-(m-trifluoromethylphenyl)piperazine, 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyrimidinyl) 1H indole, quipazine and pirenperone are essentially equipotent at both 5-HT1A and 5-HT1 sites. Thus, the 5-HT1A binding site has a pharmacological profile which, depending on the agents studied, could be significantly different from the pharmacological profile derived from total 5-HT1 binding. Drug interactions were also analyzed with canine basilar artery segments using 5-HT, 10 putative serotonergic agonists and a selective 5-HT2 antagonist, pirenperone. The maximal contraction was obtained using 5-HT (Cmax = 6.6 +/- 0.6 g). However, each of the 10 other putative 5-HT agonists elicited a less forceful contraction of the canine basilar artery.(ABSTRACT TRUNCATED AT 250 WORDS)
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D001488:Basilar Artery / Q000032:analysis / Q000187:drug effects*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007700:Kinetics; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D011985:Receptors, Serotonin / Q000032:analysis / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology; D013134:Spiperone / Q000494:pharmacology; D013764:Tetrahydronaphthalenes / Q000378:metabolism; D014316:Tritium; D014661:Vasoconstriction / Q000187:drug effects*
D010880:Piperidines; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; D014316:Tritium; D012701:Serotonin; D013134:Spiperone; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D008238:Lysergic Acid Diethylamide; C034177:pirenperone