title: Subcellular mechanisms of endothelin action in vascular system.
abstract: To elucidate the role of endothelin in the regulation of vascular function, the cellular and subcellular mechanisms for the synthesis of endothelin and the function of endothelin-receptors have been studied extensively. In this article, recent results regarding these problems are reviewed. (1) Oxidatively modified low-density-lipoprotein (LDL) reduces nitric oxide (NO) release via inhibition of the high-affinity arginine transporter of endothelial cells. (2) Endothelin-1-induced vasoconstriction is mediated by Ca2+ influx through a non-selective cation channel sensitive to 1-[beta-[3-(4-methoxyphenyl) propoxyl]-4-methoxyphenethyl]-1H-imidazole HCl (SK & F96365). (3) A distinct domain of the endothelin-receptor is required for the coupling of different G(alpha)-proteins. (4) Endothelin ET(A) receptor-mediated mitogenic activity is mediated by two pathways, one classical protein kinase C(PKC)-dependent, and the other phosphoinositide 3-kinase dependent. Both stimulate mitogen-activated protein kinase (MAPK). Endothelin ET(B) receptor-mediated mitogenic activity is also mediated by the PKC-dependent pathway. In contrast, endothelin ET(B) receptor-mediates differentiation and apoptosis via G(alpha)i coupling.
authors.affiliation: National Cardiovascular Center Research Institute, Suita, Osaka, Japan. masaki@ri.ncvc.go.jp
authors.forename: T
authors.initials: T
authors.lastname: Masaki
authors.forename: S
authors.initials: S
authors.lastname: Miwa
authors.forename: T
authors.initials: T
authors.lastname: Sawamura
authors.forename: H
authors.initials: H
authors.lastname: Ninomiya
authors.forename: Y
authors.initials: Y
authors.lastname: Okamoto
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001808:Blood Vessels / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D008078:Cholesterol, LDL / Q000494:pharmacology; D016232:Endothelins / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D008934:Mitogens; D009569:Nitric Oxide / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism; D017466:Receptors, Endothelin / Q000378:metabolism*; D014661:Vasoconstriction / Q000502:physiology*
chemical_list: D002121:Calcium Channel Blockers; D008078:Cholesterol, LDL; D016232:Endothelins; D007093:Imidazoles; D008934:Mitogens; D017466:Receptors, Endothelin; D009569:Nitric Oxide; D011494:Protein Kinases; D019204:GTP-Binding Proteins; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D002118:Calcium