Control of platelet protein kinase C activation by cyclic AMP.
Control of platelet protein kinase C activation by cyclic AMP.
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环 AMP 控制血小板蛋白激酶 C 激活。
DOI：
10.1016/0167-4889(88)90222-4
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发表时间：
1988
期刊：
影响因子：
--
通讯作者：
Schafer,AI
中科院分区：
文献类型：
--
作者：
Kroll,MH;Zavoico,GB;Schafer,AI
本实验旨在阐明环磷酸腺苷（CAMP）对血小板蛋白激酶C（PKC）激活的调控作用。双丁酰环腺苷酸可剂量依赖性地抑制4β-佛波醇12-肉豆蔻酸13-乙酸酯（PMA）或1-油酰-2-乙酰甘油（OAG）诱导的血小板聚集和分泌。这些功能活动的抑制是PMA诱导的PKC的Mr 47000底物（p47）的磷酸化的减少，通过用二丁酰cAMP预孵育血小板。这些变化也观察到血小板CAMP增加前列环素（PGI 2），毛喉素，或茶碱。ADP清除剂磷酸肌酸/肌酸磷酸激酶（CP/CPK）和环氧合酶抑制剂吲哚美辛也减少了PMA或OAG的聚集和p47磷酸化反应。双丁酰cAMP预孵育的血小板显着增强CP/CPK和吲哚美辛的抑制聚集和p47磷酸化的影响。这些结果与PMA或OAG诱导的血小板活化被分泌的ADP放大并且对分泌的ADP的反应被CAMP抑制的模型一致。此外，增加的细胞内cAMP抑制PMA或OAG诱导的p47磷酸化超过仅由CP/CPK引起的磷酸化，并且cAMP显著增强ADP去除和抑制环加氧酶阻断p47磷酸化的作用，这表明cAMP还对完整血小板中的PKC发挥非ADP介导的抑制作用。
Experiments were performed to elucidate the role of adenosine 3′:5′-cyclic monophosphate (CAMP) in the control of platelet protein kinase C (PKC) activation. Platelet aggregation and secretion in response to 4β-phorbol 12-myristate 13-acetate (PMA) or 1-oleoyl-2-acetylglycerol (OAG) were inhibited by dibutyryl cAMP in a dose-dependent manner. Inhibition of these functional activities paralleled a decrease in the PMA-induced phosphorylation of the Mr 47000 substrate (p47) of PKC by pre-incubation of platelets with dibutyryl cAMP. These changes were also observed when platelet CAMP was increased by prostacyclin (PGI2), forskolin, or theophylline. The ADP scavenger creatine phosphate /creatine phosphokinase (CP/CPK) and the cyclooxygenase inhibitor indomethacin also diminished the aggregation and p47 phosphorylation responses to PMA or OAG. Pre-incubation of platelets with dibutyryl CAMP significantly potentiated the inhibition of aggregation and p47 phosphorylation effected by CP/CPK and indomethacin. These results are consistent with the model that PMA- or OAG-induced activation of platelets is amplified by secreted ADP and that the response to secreted ADP is inhibited by CAMP. Furthermore, the findings that increased intracellular cAMP inhibits PMA- or OAG-induced p47 phosphorylation in excess of that due solely to CP/CPK, and that cAMP significantly potentiates the effects of ADP removal and inhibition of cyclooxygenase in blocking p47 phosphorylation suggest that cAMP also exerts non-ADP-mediated inhibitory effects on PKC in intact platelets.