CPI-17-deficient smooth muscle of chicken
CPI-17-deficient smooth muscle of chicken
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DOI：
10.1113/jphysiol.2004.064543
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发表时间：
2004-06-01
影响因子：
5.5
通讯作者：
Eto, M
中科院分区：
文献类型：
--
作者：
Kitazawa, T;Polzin, AN;Eto, M
动脉收缩力的 Ca2+ 敏感性是通过调节肌球蛋白磷酸酶活性来响应激动剂刺激来控制的。 CPI-17 是一种肌球蛋白磷酸酶抑制剂磷蛋白，在哺乳动物动脉中与激动剂诱导的收缩性 Ca2+ 敏化同时发生磷酸化。 CPI-17 在鸡动脉中未检测到，但在鸽子动脉中很容易检测到。为了评估 CPI-17 的作用，我们将“CPI-17 缺陷”鸡的动脉收缩力与富含 CPI-17 的兔子和鸽子的动脉收缩力进行了比较，并研究了 CPI-17 重建对鸡动脉的影响。 Ca2+ 致敏的其他主要调节/收缩蛋白在鸡和兔动脉中表达。激动剂，例如 α1 激动剂和内皮素-1，在含 Ca2+ 的生理条件下使所有物种的动脉产生显着收缩。 Ca2+ 的消耗消除了鸡的这些收缩，但部分抑制了兔和鸽子动脉的收缩。与富含 CPI-17 的组织不同，鸡动脉对 α(1) 激动剂或内皮素-1 的反应几乎没有产生 Ca2+ 致敏作用。 GTPgammaS 在鸡动脉中产生轻微的 Ca2+ 敏化作用，但与富含 CPI-17 的组织相比，这种作用明显较小。 PKC 激活剂 (PDBu) 不会在完整鸡动脉和经过 α 毒素透化的鸡动脉中产生收缩，而是减少收缩，而在富含 CPI-17 的动脉中则产生大幅收缩。 PDBu 在鸡中降低肌球蛋白轻链磷酸化，但在兔动脉中升高。将重组 CPI-17 添加到 β-七叶皂苷通透的鸡动脉中可恢复 PDBu 诱导的并增强 GTPgammaS 诱导的 Ca2+ 敏化。因此，CPI-17 对于平滑肌中 G 蛋白/PKC 介导的 Ca2+ 敏化至关重要。
Ca2+ sensitivity of arterial contractility is governed by regulating myosin phosphatase activity in response to agonist stimuli. CPI-17, a myosin phosphatase inhibitor phosphoprotein, is phosphorylated concomitantly with agonist-induced contractile Ca2+ sensitization in mammalian artery. CPI-17 has not been detected in chicken artery, but is readily detectable in pigeon artery. To evaluate a role of CPI-17, we compared contractility of the arteries of 'CPI-17-deficient' chicken with those of CPI-17-rich rabbit and pigeon, and studied the effect of CPI-17-reconstitution in chicken artery. Other major regulatory/contractile proteins for Ca2+ sensitization are expressed in both chicken and rabbit arteries. Agonists, such as an alpha1-agonist and endothelin-1, produced significant contraction in arteries of all species under physiological Ca2+-containing conditions. Depletion of Ca2+ abolished these contractions in chicken but partially inhibited them in rabbit and pigeon arteries. Unlike CPI-17-rich tissues, chicken arteries exerted little Ca2+ sensitization in response to alpha(1)-agonist or endothelin-1. GTPgammaS produced a slight Ca2+ sensitizing effect in chicken artery, but this was significantly smaller compared with CPI-17-rich tissues. A PKC activator (PDBu) did not generate but rather reduced a contraction in both intact and alpha-toxin-permeabilized chicken artery in contrast to a large contraction in CPI-17-rich arteries. Myosin light chain phosphorylation was reduced by PDBu in chicken but elevated in rabbit artery. Addition of recombinant CPI-17 into beta-escin-permeabilized chicken artery restored PDBu-induced and enhanced GTPgammaS-induced Ca2+ sensitization. Thus, CPI-17 is essential for G protein/PKC-mediated Ca2+ sensitization in smooth muscle.