Endothelin-1 induces vasoconstriction through two functionally distinct pathways in porcine coronary artery: contribution of phosphoinositide turnover.
Endothelin-1 (ET1)-induced contraction of isolated porcine coronary artery strips was previously reported to be mainly dependent on extracellular Ca2+. However, even in a Ca2+-free, EGTA-containing solution relatively high concentrations of ET1 induced a weak vasoconstriction, which was markedly but not completely inhibited by pretreatment with caffeine. Over similar dose ranges, ET1 stimulated the production of inositol phosphates in a dose-dependent manner in intact arterial tissues, which was independent of extracellular Ca2+ and was not affected by receptor blockers such as atropine, methysergide and diphenhydramine. Moreover, ET1 was shown to induce an increase in 1,2-diacylglycerol. These results indicate that the activation of ET1 receptors on porcine coronary artery smooth muscle causes phosphoinositide breakdown, leading to intracellular Ca2+ mobilization and protein kinase C activation. It is suggested that phospholipase C-mediated phosphoinositide breakdown as well as previously reported activation of voltage-dependent Ca2+ channels are involved in the mechanism of ET1-induced vasoconstriction.
Kasuya
Y
Y
Institute of Basic Medical Sciences, University of Tsukuba, Ibaraki, Japan.
Takuwa
Y
Y
Yanagisawa
M
M
Kimura
S
S
Goto
K
K
Masaki
T
T
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D016232:Endothelins; D004730:Endothelium, Vascular / Q000502:physiology*; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism; D007700:Kinetics; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D010455:Peptides / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000378:metabolism / Q000502:physiology*; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects*
D016232:Endothelins; D007295:Inositol Phosphates; D010455:Peptides; D010716:Phosphatidylinositols; D002110:Caffeine