Role of Ca2+-independent PKC in alpha(1)-adrenoceptor-mediated inotropic responses of neonatal rat hearts
Role of Ca2+-independent PKC in alpha(1)-adrenoceptor-mediated inotropic responses of neonatal rat hearts
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DOI：
10.1152/ajpheart.1997.273.3.h1113
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发表时间：
1997-09-01
影响因子：
4.8
通讯作者：
Varma, DR
中科院分区：
文献类型：
--
作者：
Deng, XF;Mulay, S;Varma, DR
我们研究了蛋白激酶C （PKC）在α(1)-肾上腺素能受体（α (1)-AR）介导的新生大鼠心肌正性肌力反应中的作用。双吲哚马来酰亚胺（BIM）是所有PKC异构体的抑制剂，可降低对苯肾上腺素和甲氧基胺的正性肌力反应，但对异丙肾上腺素没有作用。苯肾上腺素的正性肌力作用不会被Go-6976（一种Ca2+依赖性亚型的选择性抑制剂）减弱；1,2-二酰基甘油激酶抑制剂R-59949对其有增强作用。Phorbol 12,13-dibutyrate是Ca2+依赖性和非依赖性PKC异构体的激活剂，thymeleatoxin是Ca2+依赖性PKC异构体的选择性激活剂，可以抑制心肌收缩，而BIM和Go-6976可以阻止心肌收缩。BIM抑制了苯肾上腺素引起的颗粒PKC活性的增加，但没有增加磷脂酰亚苷的周转。苯肾上腺素仅诱导Ca2+非依赖性PKC-epsilon和-delta易位。这些结果表明，α (1)-AR激动剂激活Ca2+非依赖性PKC亚型在α (1)-AR介导的新生儿心肌正性肌力作用中起关键作用。
We investigated the role of protein kinase C (PKC) in alpha(1)-adrenoceptor (alpha(1)-AR)-mediated positive inotropic responses of neonatal rat myocardium. Bisindolylmaleimide (BIM), an inhibitor of all PKC isoforms, reduced the positive inotropic responses to phenylephrine and methoxamine but not to isoproterenol. The positive inotropic effect of phenylephrine was not attenuated by Go-6976, a selective inhibitor of Ca2+-dependent isoforms; it was potentiated by the 1,2-diacylglycerol kinase inhibitor R-59949. Phorbol 12,13-dibutyrate, an activator of both Ca2+-dependent and -independent PKC isoforms, as well as thymeleatoxin, a selective activator of Ca2+-dependent PKC isoforms, inhibited myocardial contractions, which were prevented by BIM and Go-6976. BIM inhibited the phenylephrine-induced increase in particulate PKC activity but not the increase in phosphatidylinositide turnover. Phenylephrine induced translocation of only Ca2+-independent PKC-epsilon and -delta. These results suggest that activation of Ca2+-independent PKC isoforms by alpha(1)-AR agonists plays a key role in alpha(1)-AR-mediated positive inotropic effect on neonatal myocardium.