Phosphatidylinositol 3-kinase modulates vascular smooth muscle contraction by calcium and myosin light chain phosphorylation-independent and -dependent pathways.
Phosphatidylinositol 3-kinase modulates vascular smooth muscle contraction by calcium and myosin light chain phosphorylation-independent and -dependent pathways.
复制标题
磷脂酰肌醇 3-激酶通过钙和肌球蛋白轻链磷酸化独立和依赖性途径调节血管平滑肌收缩。
DOI：
10.1152/ajpheart.00497.2003
复制
发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Moreland,RobertS
中科院分区：
文献类型：
--
作者：
Su,Xiaoling;Smolock,ElaineM;Marcel,KristiN;Moreland,RobertS
平滑肌收缩的调节涉及许多信号机制，包括激酶和磷酸酶反应。本研究的目的是确定一种这样的激酶，磷脂酰肌醇（PI）3-激酶，在血管平滑肌兴奋-收缩耦合中的作用。利用完整的猪颈动脉内侧条带，我们发现LY-294002对pi3激酶的抑制导致对激动剂刺激和膜去极化依赖性收缩的收缩反应的浓度依赖性降低，以及Ca2+依赖性肌球蛋白轻链（MLC）磷酸化的减少，这是开始平滑肌收缩的第一步。pi3激酶的抑制也抑制了phorbol二丁酸盐诱导的收缩，这种收缩不依赖于Ca2+或MLC磷酸化，而是依赖于蛋白激酶c。为了确定pi3激酶的Ca2+依赖性作用位点，我们确定了几种钙代谢抑制剂对ly -294002依赖性收缩抑制的影响。这些抑制剂包括硝苯地平、SK&F-96365和咖啡因。只有SK&F-96365阻断了ly -294002依赖性的收缩抑制。有趣的是，所有化合物都阻断了ly -294002依赖性的MLC磷酸化抑制。我们的研究结果表明，pi3激酶的激活参与了Ca2+和MLC磷酸化无关的收缩途径，可能涉及蛋白激酶c。此外，我们的研究结果还表明，pi3激酶的激活在受体操作的钙通道水平上参与了Ca2+依赖性信号传导。
Regulation of smooth muscle contraction involves a number of signaling mechanisms that include both kinase and phosphatase reactions. The goal of the present study was to determine the role of one such kinase, phosphatidylinositol (PI)3-kinase, in vascular smooth muscle excitation-contraction coupling. Using intact medial strips of the swine carotid artery, we found that inhibition of PI3-kinase by LY-294002 resulted in a concentration-dependent decrease in the contractile response to both agonist stimulation and membrane depolarization-dependent contractions and a decrease in Ca2+-dependent myosin light chain (MLC) phosphorylation, the primary step in the initiation of smooth muscle contraction. Inhibition of PI3-kinase also depressed phorbol dibutyrate-induced contractions, which are not dependent on either Ca2+or MLC phosphorylation but are dependent on protein kinase C. To determine the Ca2+-dependent site of action of PI3-kinase, we determined the effect of several inhibitors of calcium metabolism on LY-294002-dependent inhibition of contraction. These inhibitors included nifedipine, SK&F-96365, and caffeine. Only SK&F-96365 blocked the LY-294002-dependent inhibition of contraction. Interestingly, all compounds blocked the LY-294002-dependent inhibition of MLC phosphorylation. Our results suggest that activation of PI3-kinase is involved in a Ca2+- and MLC phosphorylation-independent pathway for contraction likely to involve protein kinase C. In addition, our results also suggest that activation of PI3-kinase is involved in Ca2+-dependent signaling at the level of receptor-operated calcium channels.
登录
查看更多内容
DOI：
10.1152/ajpcell.2000.279.2.c352
发表时间：
2000-08
期刊：
American journal of physiology. Cell physiology
影响因子：
--
作者：
I. Yamboliev;Kevin M. Wiesmann;C. Singer;J. Hedges;W. Gerthoffer
通讯作者：
I. Yamboliev;Kevin M. Wiesmann;C. Singer;J. Hedges;W. Gerthoffer
磷脂酰肌醇 3-激酶调节血管紧张素 II 诱导的胞质磷脂酶 A2 活性和血管平滑肌细胞的生长。
影响因子：
3.9
作者：
Tonous N. Silfani;E. J. Freeman
通讯作者：
E. J. Freeman
在激动剂激活透化动脉期间，恒定 Ca2 下的瞬时肌球蛋白磷酸化。
DOI：
10.1152/ajpcell.1992.263.2.c540
发表时间：
1992
期刊：
The American journal of physiology
影响因子：
--
作者：
Moreland,S;Nishimura,J;vanBreemen,C;Ahn,HY;Moreland,RS
通讯作者：
Moreland,RS
影响因子：
5
作者：
A. Mamoon;Rodney C. Baker;Jerry M. Farley
通讯作者：
A. Mamoon;Rodney C. Baker;Jerry M. Farley
用冈田酸抑制磷酸酶不会改变通透平滑肌中力和肌球蛋白轻链磷酸化之间的关系。
DOI：
10.1016/0006-291x(89)92676-4
发表时间：
1989
影响因子：
3.1
作者：
Siegman,MJ;Butler,TM;Mooers,SU
通讯作者：
Mooers,SU