Heemskerk J W, Feijge M A, Sage S O, Farndale R W
Department of Human Biology, University of Limburg, Maastricht, The Netherlands.
Biochem Pharmacol. 1997 May 9;53(9):1257-62. doi: 10.1016/s0006-2952(96)00888-x.
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 TxA2 production. U73343 was a potent inhibitor of TG-evoked arachidonic acid release, but a weak inhibitor of cytosolic phospholipase A2 (cPLA2; EC 3.1.1.4) activity. Cytosolic PLA2 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.
U73122是一种已知的磷脂酶C（PLC；EC 3.1.4.11）抑制剂。其结构类似物U73343缺乏这种活性，用作对照化合物。我们发现这两种化合物都会干扰血小板信号转导。U73122完全消除了凝血酶、凝血酶受体激活肽（TRAP）和胶原诱导的聚集。TRAP和胶原诱导的聚集也被U73343阻断，这是由于抑制血栓素A2（TxA2）生成所致。U73343是TRAP诱导的花生四烯酸释放的有效抑制剂，但对胞质磷脂酶A2（cPLA2；EC 3.1.1.4）活性的抑制作用较弱。血小板中的胞质磷脂酶A2激活涉及蛋白质酪氨酸磷酸化。U73343抑制TRAP和胶原诱导的蛋白质酪氨酸磷酸化，这可以解释其对这些物质的作用。这些数据表明，在细胞内信号通路研究中同时使用U73343和U73122时需要谨慎。
