title: Mechanism of contraction to endothelin in isolated porcine coronary artery.
abstract: To elucidate the mechanisms of action of endothelin (ET) on vascular smooth muscles, the contractile responses of the isolated porcine coronary artery to ET were precisely investigated. ET produced concentration-dependent vasoconstrictions that were not mediated by biogenic amines, arachidonate metabolites, or endothelium-derived contractile factors. The maximum response to ET was identical to the response to K+ depolarization. The vasoconstrictor activity of ET was at least one or two orders of magnitude more potent than other vasoconstrictors (BAY K 8644, histamine, acetylcholine, and prostaglandin F2 alpha) examined. The action of ET was antagonized by a dihydropyridine Ca2+ antagonist, nicardipine, in a competitive fashion. ET-induced vasoconstriction was not mediated by membrane depolarization. A small amount of ET (2 x 10(-10) M) caused a leftward shift of the concentration-response relationship for K+. ET (5 x 10(-10), 5 x 10(-8) M) accelerated 45Ca2+ uptake to the smooth muscle cells, which were inhibited by nicardipine. However, ET did not affect the specific binding of [125I]iodipine to the smooth muscle cell membrane. These results suggest that ET produces vasoconstriction via ultimately accelerating Ca2+ influx through voltage-dependent Ca2+ channels but that the binding site is distinct from that of dihydropyridines.
authors: Department of Pharmacology, University of Tsukuba, Ibaraki, Japan.
authors: Y
authors: Y
authors: Kasuya
authors: T
authors: T
authors: Ishikawa
authors: M
authors: M
authors: Yanagisawa
authors: S
authors: S
authors: Kimura
authors: K
authors: K
authors: Goto
authors: T
authors: T
authors: Masaki
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D015237:Dinoprost / Q000494:pharmacology; D016232:Endothelins; D004730:Endothelium, Vascular / Q000502:physiology*; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009529:Nicardipine / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D015220:Calcium Channels; D016232:Endothelins; D010455:Peptides; D011978:Receptors, Nicotinic; D011189:Potassium Chloride; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D006632:Histamine; D015237:Dinoprost; D009529:Nicardipine; D000109:Acetylcholine; D002118:Calcium