The mechanisms of endothelin action in vascular smooth muscle cells.
The mechanisms of actions were investigated in cultured rat aortic vascular smooth muscle A-10 cells. The A-10 cells have a single class of high affinity binding sites for ET with an apparent Mr of 65,000-75,000 on SDS-PAGE. Stimulation of cells with ET induces mobilization of Ca2+ from both intra- and extracellular pools to produce a biphasic increase in cytoplasmic free Ca2+ concentration. A dihydropyridine Ca2+ channel antagonist does not inhibit the second plateau phase of the [Ca2+]i increase which is dependent on extracellular Ca2+. ET stimulates phospholipase C to produce inositol trisphosphate and 1,2-diacylglycerol vai a pertussis toxin-insensitive G protein. These results indicate that the receptor activation by ET is coupled to phospholipase C activation and Ca2+ channel gating in vascular smooth muscle cells.
Takuwa
Y
Y
Department of Internal Medicine, University of Tsukuba, Ibaraki, Japan.
Masaki
T
T
yamashita
K
K
D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects; D002478:Cells, Cultured; D016232:Endothelins / Q000378:metabolism / Q000494:pharmacology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D037342:Pertussis Toxin; D051381:Rats; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D015220:Calcium Channels; D016232:Endothelins; D010566:Virulence Factors, Bordetella; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D037342:Pertussis Toxin; D002118:Calcium