Staurosporine and H7 attenuate ethanol-induced elevation in [Ca2+]i in cultured canine cerebral vascular smooth muscle cells.
Chronic exposure of cultured canine cerebral vascular smooth muscle cells to ethanol (10-400 mM) for 1-5 days resulted in significant concentration-dependent elevation in resting intracellular free calcium ([Ca2+]i) levels. Preincubation of these cultured vascular cells with inhibitors of protein kinase C (PKC), staurosporine and H7, induced no apparent changes from the control resting levels of [Ca2+]i. However, the increases of [Ca2+]i due to ethanol treatment were attenuated markedly by staurosporine and H7. Our data suggest that activation of PKC plays an important role in ethanol's action in producing a sustained rise in [Ca2+]i in cerebral vascular smooth muscle cells. Activation of PKC could thus play a crucial role in the pathogenesis of alcohol-induced cerebral ischemia and stroke.
Zheng
T
T
Department of Physiology, State University of New York, Health Science Center at Brooklyn, 11203, USA.
Li
W
W
Zhang
A
A
Altura
B T
BT
Altura
B M
BM
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D000431:Ethanol / Q000037:antagonists & inhibitors*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D019311:Staurosporine / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D000431:Ethanol; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D019311:Staurosporine; D002118:Calcium