5-Hydroxytryptamine (5-HT)-induced endothelium-dependent relaxation of pig coronary arteries is mediated by 5-HT receptors similar to the 5-HT1D receptor subtype.
The 5-hydroxytryptamine (5-HT) receptor mediating endothelium-dependent relaxation of pig coronary arteries was characterized using a variety of 5-HT receptor agonists and antagonists. Unrubbed (with endothelium preserved) rings precontracted by prostaglandin F2 alpha in the presence of ketanserin relaxed in an endothelium-dependent manner to 5-HT, 5-carboxamidotryptamine and 5-methoxytryptamine with about equal potency and efficacy. By comparison, bufotenine, 3-(dimethylamino)ethyl-N-methyl-1H-indole-5-methane sulfonamide, (-)-alpha-methyl-5-HT,N,N-dipropyl-5-carboxamidotryptamine and 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H indole were half-efficient and other drugs [in particular the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin] were inactive as agonists up to 0.1 mM. The effect of 5-carboxamidotryptamine was antagonized in an apparently competitive manner by 15 drugs. Among the most potent antagonists (mean pKB value) were the nonselective 5-HT receptor antagonists, methiothepin (7.30) and metergoline (6.86), the 5-HT1A/5-HT1D receptor ligand, 1-[2-(4-amino-phenyl)ethyl]-4-(3-trifluoromethylphenyl)-piperazine (7.02), the 5-HT1A/5-HT1B/5-HT1D receptor ligand, 7-trifluoromethyl-4-(4-methyl-1-piperazinyl)-pyrrolo[1,2,-a]quinoxaline 1 (6.73) and yohimbine (6.37). Selective ligands for 5-HT1A receptors were either inactive [8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide] or poorly active (spiperone, 4.44). Beta-adrenoceptor antagonists with affinity for 5-HT1A and 5-HT1B receptors weakly antagonized the effect of 5-carboxamidotryptamine (pKB values less than or equal to 5.32), as did the 5-HT1c/5-HT2 receptor antagonist, mesulergine (5.30) and the yohimbine isomer, corynanthine (4.85). Methysergide was clearly a noncompetitive antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)
Schoeffter
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Preclinical Research, Sandoz Ltd, Basel, Switzerland.
Hoyer
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D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000262:Adenylyl Cyclases / Q000032:analysis; D000818:Animals; D015237:Dinoprost / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology*; D066298:In Vitro Techniques; D011869:Radioligand Assay; D011985:Receptors, Serotonin / Q000032:analysis / Q000187:drug effects* / Q000502:physiology; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013552:Swine; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013764:Tetrahydronaphthalenes; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C047087:5-carboxamidotryptamine; D015237:Dinoprost; D000262:Adenylyl Cyclases