Importance of PKC and PI3Ks in ethanol-induced contraction of cerebral arterial smooth muscle.
We investigated the relationships of two potential intracellular signaling pathways, protein kinase C (PKC) and phosphatidylinositol 3-kinases (PI3Ks), to ethanol-induced contractions in cerebral arteries. Ethanol (20-200 mM) induces concentration-dependent constriction in isolated canine basilar arteries that is inhibited in a concentration-dependent manner by pretreatment of these vessels with 10(-9)-10(-3) M Gö-6976 (an antagonist selective for PKC-alpha and PKC-betaI), 10(-10)-10(-4) M bisindolylmaleimide I (a specific antagonist of PKC), and 10(-10)-10(-4) M wortmannin or 10(-8)-10(-2) M LY-294002 (selective antagonists of PI3Ks). Ethanol-induced increases in intracellular Ca(2+) concentration (from approximately 100 to approximately 500 nM) in canine basilar smooth muscle cells are also suppressed markedly (approximately 20-70%) in the presence of a similar concentration range of Gö-6976, bisindolymaleimide I, wortmannin, or LY-294002. This study suggests that activation of PKC isoforms and PI3Ks appears to be an important signaling pathway in ethanol-induced vasoconstriction of cerebral blood vessels.
Yang
Z W
ZW
Department of Physiology and Pharmacology, Health Science Center at Brooklyn, State University of New York, Brooklyn, New York 11203, USA.
Wang
J
J
Zheng
T
T
Altura
B T
BT
Altura
B M
BM
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D001488:Basilar Artery / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D002227:Carbazoles / Q000494:pharmacology; D002492:Central Nervous System Depressants / Q000494:pharmacology; D002867:Chromones / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008301:Maleimides / Q000494:pharmacology; D009025:Morpholines / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000201:enzymology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D020521:Stroke / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D020301:Vasospasm, Intracranial / Q000139:chemically induced / Q000378:metabolism; D000077191:Wortmannin
D000730:Androstadienes; D002118:Calcium; D002227:Carbazoles; D002492:Central Nervous System Depressants; D002867:Chromones; D004791:Enzyme Inhibitors; D000431:Ethanol; D007211:Indoles; D008301:Maleimides; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011493:Protein Kinase C; D000077191:Wortmannin; C081021:Go 6976; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C070515:bisindolylmaleimide I