Yang Z W, Wang J, Zheng T, Altura B T, Altura B M
Department of Physiology and Pharmacology, Health Science Center at Brooklyn, State University of New York, Brooklyn, New York 11203, USA.
Am J Physiol Heart Circ Physiol. 2001 May;280(5):H2144-52. doi: 10.1152/ajpheart.2001.280.5.H2144.
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.
我们研究了两种潜在的细胞内信号通路，即蛋白激酶C（PKC）和磷脂酰肌醇3激酶（PI3Ks）与乙醇诱导的脑动脉收缩之间的关系。乙醇（20 - 200 mM）可诱导离体犬基底动脉产生浓度依赖性收缩，用10⁻⁹ - 10⁻³ M Gö - 6976（PKC - α和PKC - βI的选择性拮抗剂）、10⁻¹⁰ - 10⁻⁴ M双吲哚马来酰亚胺I（PKC的特异性拮抗剂）以及10⁻¹⁰ - 10⁻⁴ M渥曼青霉素或10⁻⁸ - 10⁻² M LY - 294002（PI3Ks的选择性拮抗剂）预处理这些血管后，这种收缩会以浓度依赖性方式受到抑制。在存在类似浓度范围的Gö - 6976、双吲哚马来酰亚胺I、渥曼青霉素或LY - 294002时，乙醇诱导的犬基底平滑肌细胞内Ca²⁺浓度升高（从约100 nM升至约500 nM）也会被显著抑制（约20% - 70%）。本研究表明，PKC亚型和PI3Ks的激活似乎是乙醇诱导脑血管收缩的重要信号通路。
