Differential effects of putative protein kinase C inhibitors on contraction of rat aortic smooth muscle.
Differential effects of putative protein kinase C inhibitors on contraction of rat aortic smooth muscle.
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假定的蛋白激酶 C 抑制剂对大鼠主动脉平滑肌收缩的不同影响。
DOI：
10.1152/ajpheart.1993.264.4.h1300
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发表时间：
1993
期刊：
影响因子：
--
通讯作者：
E. Daniel
中科院分区：
文献类型：
--
作者：
Y. Shimamoto;H. Shimamoto;C. Kwan;E. Daniel
我们研究了三种可能的蛋白激酶C(PKC)抑制剂，即Calphostin C、1-(5-异喹啉磺酰基)-2-甲基哌嗪(H-7)和冬凌草碱对氯化钾、苯肾上腺素、12-O-十四酰佛波醇-13-乙酸酯(TPA)和佛波醇12，13-二丁酸酯(PDBu)引起的主动脉收缩的影响。Calphostin C以浓度依赖的方式非竞争性地抑制TPA诱导的收缩。在10(-6)M时，Calphostin C完全取消对TPA的反应，并有效地抑制PDBu引起的收缩。此浓度的Calphostin C对KCl引起的收缩无影响，但使苯肾上腺素引起的收缩反应曲线的最大张力降低35.3+/-6.6%H-7(10(-5)M)对TPA引起的收缩几乎没有影响，但对苯肾上腺素和KCl的收缩反应有明显的抑制作用。星形孢子素(10(-8)M，3×10(-8)M)可抑制KCl、苯肾上腺素和TPA的收缩反应。我们认为，星状孢子素和H-7作用于PKC的催化域，与其他蛋白激酶具有高度的序列同源性，对PKC是相对非选择性的。另一方面，与其他蛋白激酶不同的是，作用于PKC调节域的Calphostin C可能是一种相对更具选择性的PKC抑制剂。
We investigated effects of three kinds of putative protein kinase C (PKC) inhibitors, calphostin C, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7), and stauro-sporine, on aortic muscle contractions induced by KCl, phenylephrine, 12-O-tetradecanoylphorbol-13-acetate (TPA), and phorbol 12, 13-dibutyrate (PDBu). Calphostin C noncompetitively inhibited TPA-induced contractions in a concentration-dependent manner. At 10(-6) M, calphostin C completely abolished responses to TPA and also effectively inhibited PDBu-induced contractions. Such a concentration of calphostin C had no effect on KCl-induced contractions but decreased the maximal tension of phenylephrine-induced response curve by 35.3 +/- 6.6% H-7 (10(-5) M had little effect on TPA-induced contraction but significantly inhibited contractile responses to phenylephrine and KCl. Staurosporine (10(-8) M, 3 x 10(-8) M) inhibited contractile responses to KCl, phenylephrine, and TPA. We suggest that staurosporine and H-7, which are known to act on the catalytic domain of PKC carrying high degree of sequence homology with other protein kinases, are relatively nonselective for PKC. On the other hand, calphostin C acting on the regulatory domain of PKC, which is distinct from other protein kinases, may serve as a relatively more selective PKC inhibitor.