...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>American Journal of Physiology >Signal-transduction pathways that regulate smooth muscle function I. Signal transduction in phasic (esophageal) and tonic (gastroesophageal sphincter) smooth muscles.
【24h】

Signal-transduction pathways that regulate smooth muscle function I. Signal transduction in phasic (esophageal) and tonic (gastroesophageal sphincter) smooth muscles.

机译：调节平滑肌功能的信号转导途径I.相位（食道）和强直（胃食管括约肌）平滑肌的信号转导。

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

Contraction of esophageal (Eso) and lower esophageal sphincter (LES) circular muscle depends on distinct signal-transduction pathways. ACh-induced contraction of Eso muscle is linked to phosphatidylcholine metabolism, production of diacylglycerol and arachidonic acid (AA), and activation of the Ca(2+)-insensitive PKCepsilon. Although PKCepsilon does not require Ca(2+) for activation, either influx of extracellular Ca(2+) or release of Ca(2+) from stores is needed to activate the phospholipases responsible for hydrolysis of membrane phospholipids and production of second messengers, which activate PKCepsilon. In contrast, the LES uses two distinct intracellular pathways: 1) a PKC-dependent pathway activated by low doses of agonists or during maintenance of spontaneous tone, and 2) a Ca(2+)-calmodulin-myosin light chain kinase (MLCK)-dependent pathway activated in response to maximally effective doses of agonists during the initial phase of contraction. The Ca(2+) levels, released by agonist-induced activity of phospholipase C, determine which contractile pathway is activated in the LES. The Ca(2+)-calmodulin-MLCK-dependent contractile pathway has been well characterized in a variety of smooth muscles. The steps linking activation of PKC to myosin light chain (MLC20) phosphorylation and contraction, however, have not been clearly defined for LES, Eso, or other smooth muscles. In addition, in LES circular muscle, a low-molecular weight pancreatic-like phospholipase A2 (group I PLA2) causes production of AA, which is metabolized to prostaglandins and thromboxanes. These AA metabolites act on receptors linked to heterotrimeric G proteins to induce activation of phospholipases and production of second messengers to maintain contraction of LES circular muscle. We have examined the signal-transduction pathways activated by PGF(2alpha) and by thromboxane analogs during the initial contractile phase and found that these pathways are the same as those activated by other agonists. In response to low doses of agonists or during maintenance of tone, presumably due to low levels of calcium release, a PKC-dependent pathway is activated, whereas at high doses of PGF(2alpha) and thromboxane analogs, in the initial phase of contraction, calmodulin is activated, PKC activity is reduced, and contraction is mediated, in part, through a Ca(2+)-calmodulin-MLCK-dependent pathway. The PKC-dependent signaling pathways activated by PGF(2alpha) and by thromboxanes during sustained LES contraction, however, remain to be examined, but preliminary data indicate that a distinct PKC-dependent pathway may be activated during maintenance of tonic contraction, which is different from the one activated during the initial contractile response. The initial contractile response to low levels of agonists depends on activation of G(q). Sustained contraction in response to PGF(2alpha) may involve activation of the monomeric G protein RhoA, because the contraction is inhibited by the RhoA-kinase antagonist Y27632. This shift in signal-transduction pathways between initial and sustained contraction has been recently reported in intestinal smooth muscle.
机译：食管（Eso）和食管下括约肌（LES）环形肌肉的收缩取决于不同的信号转导途径。 ACh诱导的Eso肌肉收缩与磷脂酰胆碱的代谢，二酰基甘油和花生四烯酸（AA）的产生以及Ca（2+）不敏感的PKCepsilon的激活有关。尽管PKCepsilon不需要激活Ca（2+），但需要注入细胞外Ca（2+）或从存储中释放Ca（2+）来激活负责水解膜磷脂和产生第二信使的磷脂酶，激活PKCepsilon。相反，LES使用两种不同的细胞内途径：1）由低剂量激动剂激活或在维持自发音调期间激活的PKC依赖性途径，以及2）Ca（2 +）-钙调蛋白-肌球蛋白轻链激酶（MLCK）在收缩的初始阶段，对最大有效剂量的激动剂起反应，激活了依赖依赖性途径。通过激动剂诱导的磷脂酶C的活性释放的Ca（2+）水平确定在LES中激活了哪个收缩途径。 Ca（2 +）-钙调蛋白-MLCK依赖的收缩途径已经在各种平滑肌中得到了很好的表征。但是，对于LES，Eso或其他平滑肌，尚未明确定义将PKC激活与肌球蛋白轻链（MLC20）磷酸化和收缩联系起来的步骤。此外，在LES环形肌中，低分子量的胰腺样磷脂酶A2（I类PLA2）引起AA的产生，并被代谢为前列腺素和血栓烷。这些AA代谢物作用于与异三聚体G蛋白相连的受体，从而诱导磷脂酶的活化和第二信使的产生，从而维持LES环形肌的收缩。我们已经检查了在初始收缩期由PGF（2alpha）和血栓烷类似物激活的信号转导通路，发现这些通路与其他激动剂激活的通路相同。响应低剂量的激动剂或维持口气期间（大概是由于钙释放水平低），PKC依赖性途径被激活，而高剂量的PGF（2α）和血栓烷类似物在收缩初期，钙调蛋白被激活，PKC活性降低，并且收缩部分通过Ca（2 +）-钙调蛋白-MLCK依赖性途径介导。由PGF（2alpha）和血栓烷在持续LES收缩过程中激活的PKC依赖信号通路尚待研究，但初步数据表明，在维持补品收缩过程中可能激活了独特的PKC依赖途径，这是不同的从最初的收缩反应过程中激活的对低水平激动剂的初始收缩反应取决于G（q）的激活。对PGF（2alpha）的持续收缩可能涉及单体G蛋白RhoA的激活，因为该收缩受到RhoA激酶拮抗剂Y27632的抑制。最近已经在肠道平滑肌中报道了初始收缩和持续收缩之间信号传导途径的这种转变。

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