Importance of PKC and PI3Ks in ethanol-induced contraction of cerebral arterial smooth muscle

Abstract

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-α and PKC-βI), 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 Ca2+ concentration (from ∼100 to ∼500 nM) in canine basilar smooth muscle cells are also suppressed markedly (∼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.