Crouch M F, Lapetina E G
Department of Molecular Biology, Burroughs Wellcome Co., Research Triangle Park, North Carolina 27709.
J Biol Chem. 1989 Jan 5;264(1):584-8.
Several different agonists, among them alpha-thrombin, platelet-activating factor, vasopressin, thromboxane A2, and endoperoxides, activate platelets to aggregate and secrete granular contents. Each of these agents is thought to act by inducing the turnover of inositol phospholipids and generating the second messenger molecules inositol 1,4,5-trisphosphate and 1,2-diacylglycerol. However, within minutes, the action of these agonists desensitizes. We have studied the characteristics of this desensitization process for the agonists mentioned above in an attempt to clarify the mechanisms involved. Our results show that two different pathways of desensitization exist, one that is mediated by protein kinase C and another that is independent of this enzyme. In addition, the contribution of these pathways to desensitization differs for the agonists studied. Our data suggest that partial agonists and strong agonists differ in the rate at which the primary response is desensitized rather than in their ability to couple to phospholipase C.
几种不同的激动剂，包括α-凝血酶、血小板活化因子、血管加压素、血栓素A2和内过氧化物，可激活血小板聚集并分泌颗粒内容物。据认为，这些激动剂中的每一种都是通过诱导肌醇磷脂的周转并生成第二信使分子肌醇1,4,5-三磷酸和1,2-二酰甘油来发挥作用的。然而，几分钟内，这些激动剂的作用就会脱敏。我们研究了上述激动剂脱敏过程的特征，试图阐明其中涉及的机制。我们的结果表明，存在两种不同的脱敏途径，一种由蛋白激酶C介导，另一种独立于该酶。此外，这些途径对脱敏的贡献因所研究的激动剂而异。我们的数据表明，部分激动剂和强效激动剂在初级反应脱敏的速率上有所不同，而不是在它们与磷脂酶C偶联的能力上有所不同。
