Schächtele C, Seifert R, Osswald H
Goedecke Forschungsinstitut, Biochemische Pharmakologie, Freiburg, F.R.G.
Biochem Biophys Res Commun. 1988 Feb 29;151(1):542-7. doi: 10.1016/0006-291x(88)90628-6.
Thrombin, 1-oleoyl-2-acetyl-rac-glycerol (OAG), cis- or trans-octadecadienoic acids (linoleic and linolelaidic acid) and the synergistic combination of octadecadienoic acids plus OAG lead to the activation of gel-filtered human platelets, i.e. aggregation via protein kinase C (PKC). Platelet activation by thrombin was only slightly suppressed by polymyxin B, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7) or staurosporine, all being potent inhibitors of PKC in vitro. The OAG-induced aggregation, however, was strongly inhibited by H-7 or staurosporine but not by polymyxin B. In contrast, octadecadienoic acid-induced aggregation was substantially inhibited only by polymyxin B. Synergistic activation by OAG plus octadecadienoic acids was strongly suppressed by all three PKC inhibitors. Our results indicate (1) that the ability of various compounds to inhibit PKC in vitro does not correlate with their inhibitory effects in intact cells and (2) that platelet activation induced by various PKC activators exhibits differential PKC-inhibitor sensitivity.
凝血酶、1-油酰基-2-乙酰基-消旋甘油（OAG）、顺式或反式十八碳二烯酸（亚油酸和反式亚油酸）以及十八碳二烯酸与OAG的协同组合可导致凝胶过滤的人血小板活化，即通过蛋白激酶C（PKC）介导聚集。凝血酶诱导的血小板活化仅被多粘菌素B、1-（5-异喹啉磺酰基）-2-甲基哌嗪（H-7）或星形孢菌素轻微抑制，这些在体外均为有效的PKC抑制剂。然而，OAG诱导的聚集被H-7或星形孢菌素强烈抑制，但不被多粘菌素B抑制。相反，十八碳二烯酸诱导的聚集仅被多粘菌素B显著抑制。OAG与十八碳二烯酸的协同活化被所有三种PKC抑制剂强烈抑制。我们的结果表明：（1）各种化合物在体外抑制PKC的能力与其在完整细胞中的抑制作用不相关；（2）各种PKC激活剂诱导的血小板活化表现出不同的PKC抑制剂敏感性。
