Human platelet activation is inhibited upstream of the activation of phospholipase A(2) by U73343

被引：7

作者：

Heemskerk, JWM

Feijge, MAH

Sage, SO

Farndale, RW

机构：

[1] UNIV CAMBRIDGE, PHYSIOL LAB, CAMBRIDGE CB2 3EG, ENGLAND

[2] UNIV LIMBURG, DEPT HUMAN BIOL, NL-6200 MD MAASTRICHT, NETHERLANDS

[3] UNIV LIMBURG, DEPT BIOCHEM, NL-6200 MD MAASTRICHT, NETHERLANDS

[4] UNIV CAMBRIDGE, DEPT BIOCHEM, CAMBRIDGE CB2 1QW, ENGLAND

来源：

BIOCHEMICAL PHARMACOLOGY | 1997年 / 53卷 / 09期

基金：

英国惠康基金;

关键词：

cytosolic calcium concentration; phospholipase A(2); U73122; U73343; platelet; tyrosine phosphorylation;

D O I：

10.1016/S0006-2952(96)00888-X

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

U73122 is known as an inhibitor of phospholipase C (PLC; EC 3.1.4.11). Its close structural analogue, U73343, lacks this activity and is used as a control compound. We have found that both compounds interfere with platelet signal transduction. U73122 completely abolished aggregation evoked by thrombin, TG, and collagen. Aggregation evoked by TG and collagen was also blocked by U73343, an effect due to inhibition of TxA(2) production. U73343 was a potent inhibitor of TG-evoked arachidonic acid release, but a weak inhibitor of cytosolic phospholipase A(2) (cPLA(2); EC 3.1.1.4) activity. Cytosolic PLA(2) activation in platelets involves protein tyrosine phosphorylation. U73343 inhibited TG- and collagen-evoked protein tyrosine phosphorylation, which can thus explain its action against these agents. These data indicate that caution is needed when using U73343 along with U73122 in the study of intracellular signalling pathways. (C) 1997 Elsevier Science Inc.

引用

页码：1257 / 1262

页数：6

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