A hypothesis for the mechanism of receptor and G-protein-dependent enhancement of vascular smooth muscle myofilament Ca2+ sensitivity.
A hypothesis for the mechanism of receptor and G-protein-dependent enhancement of vascular smooth muscle myofilament Ca2+ sensitivity.
复制标题
受体和 G 蛋白依赖性增强血管平滑肌肌丝 Ca2+ 敏感性的机制假设。
DOI：
10.1139/y94-205
复制
发表时间：
1994
影响因子：
2.1
通讯作者：
Moreland,RS
中科院分区：
文献类型：
--
作者：
Rokolya,A;Ahn,HY;Moreland,S;vanBreemen,C;Moreland,RS
激动剂激活增强平滑肌肌丝Ca 2+敏感性。伴随受体刺激的力增加（超过单独的Ca 2+）需要GTP，并被GDPβS逆转，证明了G蛋白依赖性。蛋白激酶C（PKC）激活剂，例如佛波酯、模拟剂和PKC抑制剂，可以阻断激动剂诱导的Ca 2+敏感性增加，表明PKC在调节Ca 2+敏感性中发挥作用。肌球蛋白轻链（MLC）磷酸化水平瞬时增加激动剂刺激，但MLC磷酸化的稳态水平是类似的，在响应单独的钙离子。因此，G-蛋白介导的抑制MLC磷酸酶可能占力发展的初始增加，但不是稳态力的增加。与MLC相反，在完整血管平滑肌的激动剂刺激期间维持钙调蛋白磷酸化水平。我们建议，刺激平滑肌膜去极化增加MLC磷酸化，但由于非磷酸化的钙调蛋白的抑制，只有一部分磷酸化的跨桥连接到肌动蛋白。激动剂刺激产生相同稳态水平的MLC磷酸化，但也通过PKC依赖性途径导致钙调蛋白磷酸化。因此，在激动剂刺激过程中，所有磷酸化的横桥可以与肌动蛋白相互作用，从而产生明显更大水平的力。关键词：β毒素，透化平滑肌，钙，钙调蛋白，磷酸化，致敏，蛋白激酶C，肠系膜动脉，内皮素。
Agonist activation enhances smooth muscle myofilament Ca2+sensitivity. The increased force accompanying receptor stimulation (over Ca2+alone) requires GTP and is reversed by GDPβS, demonstrating a G-protein dependence. Protein kinase C (PKC) activators, such as phorbol esters, mimic and PKC inhibitors block the agonist-induced increase in Ca2+sensitivity, suggesting a role for PKC in the regulation of Ca2+sensitivity. Myosin light chain (MLC) phosphorylation levels are transiently increased by agonist stimulation, but steady-state levels of MLC phosphorylation are similar to those in response to Ca2+alone. Thus, G-protein-mediated inhibition of MLC phosphatase may account for the initial increase in force development but not the increase in steady-state force. In contrast to MLC, calponin phosphorylation levels are maintained during agonist stimulation of intact vascular smooth muscle. We propose that stimulation of smooth muscle by membrane depolarization increases MLC phosphorylation, but as a result of inhibition by unphosphorylated calponin only a portion of the phosphorylated cross bridges attach to actin. Agonist stimulation produces the same steady-state level of MLC phosphorylation but also leads to calponin phosphorylation via a PKC-dependent pathway. Thus, during agonist stimulation, all phosphorylated cross bridges can interact with actin, thereby generating significantly greater levels of force.Key words: β-toxin, permeabilized smooth muscle, calcium, calponin, phosphorylation, sensitization, protein kinase C, mesenteric artery, endothelin.