Savi P, Pflieger A M, Herbert J M
SANOFI Recherche, Haemobiology Research Department, Toulouse, France.
Blood Coagul Fibrinolysis. 1996 Mar;7(2):249-52. doi: 10.1097/00001721-199603000-00035.
In rat platelets, basal cAMP level did not vary significantly during ADP-induced aggregation. In the same conditions, no variation in the cAMP content was observed in platelets from rats treated with clopidogrel, whereas ADP-induced aggregation was totally inhibited. ADP decreased cAMP level in control prostacyclin- or forskolin-stimulated platelets whereas, in treated platelets, adenylyl cyclase down-regulation was strongly inhibited. SQ 22536 (500 microM), an inhibitor of adenylyl cyclase, strongly reduced the cAMP content of both control and treated platelets but did not reverse the anti-aggregating activity of clopidogrel, showing that inhibition of ADP-induced adenylyl cyclase down-regulation in treated platelets was not responsible for the anti-aggregating effect of clopidogrel. Similar results were obtained in rabbit platelets. These results therefore demonstrate that cAMP is not an important second messenger for ADP-induced platelet aggregation and suggest that another activating pathway, linked to the low affinity ADP receptor present on the platelet surface might be involved in the aggregation process.
在大鼠血小板中，ADP诱导的聚集过程中基础cAMP水平无显著变化。在相同条件下，用氯吡格雷处理的大鼠血小板中未观察到cAMP含量的变化，而ADP诱导的聚集被完全抑制。ADP降低了对照中前列环素或福斯可林刺激的血小板中的cAMP水平，而在处理过的血小板中，腺苷酸环化酶的下调受到强烈抑制。腺苷酸环化酶抑制剂SQ 22536（500微摩尔）强烈降低了对照和处理过的血小板中的cAMP含量，但并未逆转氯吡格雷的抗聚集活性，表明处理过的血小板中ADP诱导的腺苷酸环化酶下调的抑制并非氯吡格雷抗聚集作用的原因。在兔血小板中也得到了类似结果。因此，这些结果表明cAMP不是ADP诱导血小板聚集的重要第二信使，并提示与血小板表面存在的低亲和力ADP受体相关的另一条激活途径可能参与了聚集过程。
