HUMAN PLATELET ACTIVATION IS INHIBITED UPSTREAM OF THE ACTIVATION OF PHOSPHOLIPASE A(2) BY U73343

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 use d as a control compound. We have found that both compounds interfere w ith platelet signal transduction. U73122 completely abolished aggregat ion evoked by thrombin, TG, and collagen. Aggregation evoked by TG and collagen was also blocked by U73343, an effect due to inhibition of T xA(2) production. U73343 was a potent inhibitor of TG-evoked arachidon ic acid release, but a weak inhibitor of cytosolic phospholipase A(2) (cPLA(2); EC 3.1.1.4) activity. Cytosolic PLA(2) activation in platele ts involves protein tyrosine phosphorylation. U73343 inhibited TG- and collagen-evoked protein tyrosine phosphorylation, which can thus expl ain its action against these agents. These data indicate that caution is needed when using U73343 along with U73122 in the study of intracel lular signalling pathways. (C) 1997 Elsevier Science Inc.