Regulation of platelet phospholipase C.
Regulation of platelet phospholipase C.
复制标题
血小板磷脂酶的调节 C.
DOI：
10.1098/rstb.1988.0078
复制
发表时间：
1988
期刊：
影响因子：
--
通讯作者：
Tarver,AP
中科院分区：
文献类型：
--
作者：
Rittenhouse,SE;Banga,HS;Sasson,JP;King,WG;Tarver,AP
我们研究了影响人血小板中磷脂酶 C 活化的因素。将血小板预先暴露于刺激蛋白激酶 C 的佛波酯中，可抑制磷脂酶 C 响应各种受体导向激动剂（包括 x-和 y-凝血酶以及血栓素 A2 类似物）的激活。这种激活已通过测量累积的InsP3（包括Ins(1,4,5)P3和Ins(1,3,4)P3）和PtdOH来测定。 Ca2+离子载体不能克服抑制作用，并且阻断或模拟Na+-H+交换的物质既不阻断也不模拟这些抑制作用。环 AMP 和环 GMP 以及其他已知可抑制磷脂酶 C 活化的药物不会在暴露于佛波酯的血小板中积聚。虽然佛波酯对 InsP3 积累的部分影响可以通过 5-磷酸单酯酶活性来解释，但也可能对磷脂酶 C 产生更直接的影响，并提供主要的抑制途径。我们检查了腺苷酸环化酶相关的 G1 和“Gp”激活的磷脂酶 C 对百日咳毒素衍生酶（S1 原体）对皂苷透化血小板进行抑制性 ADP 核糖基化的敏感性。 S1 可将α-凝血酶对腺苷酸环化酶的作用抑制高达 50%，此时几乎检测不到磷脂酶 C 的抑制。血栓素 A2 类似物不影响腺苷酸环化酶 (G1)，但会刺激磷脂酶 C； Sr 不会削弱这种作用，因此我们认为佛波酯对磷脂酶 C 活化的抑制作用主要不是由对 G1 的作用介导的。
We have investigated factors affecting the activation of phospholipase C in human platelets. Prior exposure of platelets to phorbol esters that stimulate protein kinase C inhibits the activation of phospholipase C in response to a variety of receptor-directed agonists, including x- and y-thrombin and thromboxane A2analogues. Such activation has been assayed by measurements of accumulated InsP3(including Ins(l,4,5)P3and Ins(l,3,4)P3) and PtdOH. Inhibition is not overcome by Ca2+ionophores, and substances that block or mimic Na+-H + exchange neither block nor mimic these inhibitory effects. Cyclic AMP and cyclic GMP, other agents known to inhibit phospholipase C activation, do not accumulate in platelets exposed to phorbol esters. Although a portion of the effects of phorbol ester on InsP3accumulation may be explained by 5-phosphomonoesterase activity, it is likely that more direct effects on phospholipase C are being exerted as well, and contribute the major inhibitory route. We have examined the susceptibility of adenylyl cyclase-associated G1and ‘Gp’- activated phospholipase C to inhibitory ADP-ribosylation by pertussis toxin-derived enzyme (S1protomer) administered to saponin-permeabilized platelets. The effects of a-thrombin on adenylyl cyclase can be inhibited by up to 50% by S1at which point inhibition of phospholipase C is barely detectable. Thromboxane A2analogues, which do not affect adenylyl cyclase (G1), stimulate phospholipase C; this effect is not impaired by Sr We therefore propose that the inhibitory effects of phorbol esters on the activation of phospholipase C are not mediated primarily by effects on G1.