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 ar teries that is inhibited in a concentration-dependent manner by pretreatmen t of these vessels with 10(-9)-10(-3) M Go-6976 (an antagonist selective fo r PKC-alpha and PKC-betaI), 10(-10)-10(-4) M bisindolylmaleimide I (a speci fic antagonist of PKC betaI), and 10(-1) -10(-4) M wortmannin or 10(-8)-10( -2) M LY-294002 (selective antagonists of PI3Ks). Ethanol-induced increases in intracellular Ca2+ concentration (from similar to 100 to similar to 500 nM) in canine basilar smooth muscle cells are also suppressed markedly (si milar to 20-70%) in the presence of a similar concentration range of Go-697 6, 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.