Endothelin-1 and insulin activate the steady-state voltage dependent R-type Ca2+ channel in aortic smooth muscle cells via a pertussis toxin and cholera toxin sensitive G-protein.
In single rabbit aortic smooth muscle cells, and at a concentration known to induce a maximum sustained increase of intracellular Ca2+ via activation of the steady-state voltage dependent R-type Ca2+ channels, endothelin-1 (10(-7) M) and insulin (80 microU/ml) were found to induce a sustained increase in cytosolic free Ca2+ ([Ca]i) levels that was significantly attenuated by pre-treatment with either pertussis toxin (PTX), cholera toxin (CTX) or removal of extracellular Ca2+. However, both PTX and CTX failed to inhibit the sustained depolarization-evoked sustained Ca2+ influx and [Ca]i elevation via activation of the R-type Ca2+ channels. Moreover, ET-1 and insulin-evoked sustained increases in Ca2+ influx were not attenuated by the selective PKC inhibitor, bisindolylmaleimide (BIS), or the specific L-type Ca2+ channel blocker, nifedipine, but were completely reversed by the R-type Ca2+ channel blocker, (-) PN 200-110 (isradipine). These data suggest that both insulin and ET-1 activate the nifedipine-insensitive but isradipine-sensitive steady state voltage dependent R-type Ca2+ channels present on rabbit VSMCs and these channels are directly coupled to PTX and CTX sensitive G protein(s).
Bkaily
G
G
Department of Pharmacology, Faculty of Medicine, Université de Sherbrooke, Québec, Canada.
Naik
R
R
Jaalouk
D
D
Jacques
D
D
Economos
D
D
D'Orléans-Juste
P
P
Pothier
P
P
D000818:Animals; D001011:Aorta; D002110:Caffeine / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism*; D002772:Cholera Toxin / Q000494:pharmacology*; D019332:Endothelin-1 / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000502:physiology*; D007211:Indoles / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology*; D017136:Ion Transport / Q000187:drug effects; D017275:Isradipine / Q000494:pharmacology; D008301:Maleimides / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology; D037342:Pertussis Toxin; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D011817:Rabbits; D012433:Ryanodine / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D015220:Calcium Channels; D019332:Endothelin-1; D007211:Indoles; D007328:Insulin; D008301:Maleimides; D010566:Virulence Factors, Bordetella; D012433:Ryanodine; D002110:Caffeine; D002772:Cholera Toxin; D037342:Pertussis Toxin; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D009543:Nifedipine; C088060:bisindolylmaleimide; D017275:Isradipine