Hatmi M, Rotilio D, Haye B, Antonicelli F, Joseph D, Vargaftig B B
Eur J Pharmacol. 1986 Dec 16;132(2-3):219-28. doi: 10.1016/0014-2999(86)90608-4.
We have previously demonstrated that arachidonic acid (AA) and the stable cyclic endoperoxide analogue (U46619) desensitize human platelets at a common site, which is sensitive to endoperoxides/thromboxane receptor antagonists. We now report on the influence of agents which evaluate intracellular levels of platelet adenosine 3',5'-cyclic monophosphate (cAMP) on AA- and U46619-induced platelet desensitization. Prostaglandin E1, prostacyclin, carbacyclin, forskolin or dibutyryl cAMP prevented platelet activation by and desensitization to AA and to U46619 under conditions where the formation of thromboxane B2 was not significantly modified. Inhibition of platelet activation (aggregation and secretion) required a lower increase of the cAMP content than was needed to inhibit desensitization, confirming previous findings that desensitization to and by AA or U46619 are independent from the platelet release reaction. Together, these results indicate that AA-induced desensitization can be modulated by the adenylate cyclase/cAMP system acting at a site distinct from the known mechanisms of Ca2+ sequestration. This site is shared by the AA metabolite responsible for desensitization and by U46619 and is related to their common platelet membrane receptor.
我们之前已经证明，花生四烯酸（AA）和稳定的环内过氧化物类似物（U46619）在一个共同位点使人类血小板脱敏，该位点对内过氧化物/血栓素受体拮抗剂敏感。我们现在报告评估血小板3',5'-环磷酸腺苷（cAMP）细胞内水平的试剂对AA和U46619诱导的血小板脱敏的影响。在血栓素B2的形成没有显著改变的条件下，前列腺素E1、前列环素、卡前列环素、福斯高林或二丁酰cAMP可防止血小板被AA和U46619激活并脱敏。抑制血小板激活（聚集和分泌）所需的cAMP含量增加低于抑制脱敏所需的增加量，这证实了之前的发现，即对AA或U46619的脱敏与血小板释放反应无关。总之，这些结果表明，AA诱导的脱敏可由腺苷酸环化酶/cAMP系统在一个不同于已知Ca2+螯合机制的位点进行调节。该位点由负责脱敏的AA代谢物以及U46619共享，并且与它们共同的血小板膜受体有关。
