Rho‐kinase inhibitor inhibits both myosin phosphorylation‐dependent and ‐independent enhancement of myofilament Ca2+ sensitivity in the bovine middle cerebral artery

Rho‐kinase inhibitor inhibits both myosin phosphorylation‐dependent and ‐independent enhancement of myofilament Ca2+ sensitivity in the bovine middle cerebral artery
复制标题

Rho激酶抑制剂抑制牛大脑中动脉肌球蛋白磷酸化依赖和独立的肌丝Ca2+敏感性增强

DOI:
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发表时间:
2003
影响因子:
7.3
通讯作者:
H. Kanaide
H. Kanaide
中科院分区:
医学2区
文献类型:
--
作者:
Y. Maeda;K. Hirano;J. Nishimura;Tomio Sasaki;H. Kanaide

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在牛大脑中动脉研究了Rho激酶在平滑肌收缩器Ca ~(2+)敏感化中的作用。U46619是一种血栓素A2类似物,与118 mM K+相比,诱导了更大的持续收缩,但[Ca 2 +]i升高较小。肌球蛋白轻链(MLC)的磷酸化水平在收缩的初始阶段得到的高于118 mM K+,此后,它逐渐下降到一个相当的水平在后期。在U46619诱导的收缩的稳态期间,Y27632(10 μM),一种Rho激酶抑制剂,部分抑制[Ca 2 +]i,尽管它显著抑制张力和MLC磷酸化。MLC激酶抑制剂Wortmannin(10 μM)对[Ca 2 +]i无显著影响,但可完全抑制MLC磷酸化,部分抑制张力。因此,抗渥曼青霉素的张力发展与MLC磷酸化无关,并且该组分完全被Y27632抑制。总之,U46619以依赖和独立于牛大脑中动脉中MLC磷酸化的方式增强Ca 2+敏感性。两种Ca 2+敏化机制均可被Rho激酶抑制剂抑制。
The role of Rho kinase in Ca2+ sensitization of the contractile apparatus in smooth muscle was investigated in the bovine middle cerebral artery. U46619, a thromboxane A2 analog, induced a greater sustained contraction with a smaller [Ca2+]i elevation than that seen with 118 mM K+. The level of myosin light chain (MLC) phosphorylation obtained in the initial phase of the contraction was higher than that seen with 118 mM K+; thereafter, it gradually declined to a comparable level in the late phase. During the steady state of the U46619‐induced contraction, Y27632 (10 μM), a Rho‐kinase inhibitor, partially inhibited [Ca2+]i, although it substantially inhibited tension and MLC phosphorylation. Wortmannin (10 μM), an MLC kinase inhibitor, had no significant effect on [Ca2+]i, but it completely inhibited MLC phosphorylation and partially inhibited tension. The wortmannin‐resistant tension development was thus not associated with MLC phosphorylation, and this component was completely inhibited by Y27632. In conclusion, U46619 enhanced Ca2+ sensitivity in a manner both dependent and independent of MLC phosphorylation in the bovine middle cerebral artery. Both mechanisms of Ca2+ sensitization can be inhibited by the Rho‐kinase inhibitor.
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
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DOI: --
发表时间: 1990
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