• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>American Journal of Physiology >Convergence of Ca2+-desensitizing mechanisms activated by forskolin and phenylephrine pretreatment, but not 8-bromo-cGMP.
【24h】

Convergence of Ca2+-desensitizing mechanisms activated by forskolin and phenylephrine pretreatment, but not 8-bromo-cGMP.

机译：佛司可林和去氧肾上腺素预处理激活的Ca2 +脱敏机制的收敛性，但8-溴-cGMP则没有。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Contractile stimuli can sensitize myosin to Ca2+ by activating RhoA kinase (ROK) and PKC that inhibit myosin light chain phosphatase (MLCP) activity. Relaxant stimuli, acting through PKA and PKG (cyclic nucleotide-dependent protein kinases), and pretreatment with contractile agents such as phenylephrine (PE), can desensitize myosin to Ca2+. It is unknown precisely how these stimuli cause Ca2+ desensitization. To test the hypothesis that PKA, PKG, and PE pretreatment signaling systems converge to cause relaxation by inhibition of ROK in intact, isolated tissues, we examined the effects of forskolin (FSK; PKA activation), 8-bromo-cGMP (8br-cGMP; PKG activation), and PE pretreatment on KCl-induced force maintenance in rabbit arteries, a response nearly completely dependent on ROK activation. PE pretreatment and agents activating PKA and PKG caused Ca2+ desensitization by inhibiting KCl-induced tonic force and MLC phosphorylation without inhibiting intracellular [Ca2+]. At pCa 5 in beta-escin-permeabilizedmuscle, FSK and 8b-cGMP accelerated the relaxation rate when tissues were returned to pCa 9, suggesting that both agents can elevate MLCP activity. However, a component of the Ca2+ desensitization attributed to PKG activation in intact tissues appeared to involve a MLC phosphorylation-independent component. Inhibition of KCl-induced tonic force by the ROK inhibitor, Y-27632, and by PE pretreatment, were synergistically potentiated by 8b-cGMP, but not FSK. FSK and PE pretreatment, but not 8b-cGMP, inhibited the KCl-induced increase in site-specific myosin phosphatase target protein-1 phosphorylation at Thr853. These data support the hypothesis that PKA and PE pretreatment converge on a common Ca2+-desensitization pathway, but that PKG can act by a mechanism different from that activated by PKA and PE pretreatment.
机译：收缩性刺激可以通过激活RhoA激酶（ROK）和PKC来抑制肌球蛋白轻链磷酸酶（MLCP）的活性，从而使肌球蛋白对Ca2 +敏感。松弛刺激通过PKA和PKG（环状核苷酸依赖性蛋白激酶）起作用，并用收缩剂如去氧肾上腺素（PE）预处理，可使肌球蛋白对Ca2 +脱敏。这些刺激是如何引起Ca2 +脱敏的确切原因尚不清楚。为了检验PKA，PKG和PE预处理信号系统收敛以通过抑制完整完整的分离组织中的ROK引起松弛的假说，我们研究了福司可林（FSK; PKA激活），8-溴-cGMP（8br-cGMP ; PKG激活）和PE预处理对KCl诱导的兔动脉维持力的反应几乎完全取决于ROK激活。 PE预处理和激活PKA和PKG的试剂可通过抑制KCl诱导的张力和MLC磷酸化而不抑制细胞内[Ca2 +]引起Ca2 +脱敏。在β-七叶皂素通透性肌肉中的pCa 5处，当组织返回pCa 9时，FSK和8b-cGMP加快了松弛速率，表明这两种药物均可提高MLCP活性。但是，归因于完整组织中PKG活化的Ca2 +脱敏成分似乎与MLC磷酸化无关成分有关。 Rb抑制剂Y-27632和PE预处理对KCl诱导的张力的抑制作用由8b-cGMP协同增强，但对FSK则没有协同作用。 FSK和PE预处理，但不抑制8b-cGMP，抑制了KCl诱导的Thr853位点特异性肌球蛋白磷酸酶靶蛋白1磷酸化的增加。这些数据支持以下假设：PKA和PE预处理在一条常见的Ca2 +脱敏途径上收敛，但是PKG可以通过不同于PKA和PE预处理激活的机制起作用。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号