Defective smooth muscle regulation in cGMP kinase I-deficient mice
Defective smooth muscle regulation in cGMP kinase I-deficient mice
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DOI：
10.1093/emboj/17.11.3045
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发表时间：
1998-06-01
期刊：
影响因子：
11.4
通讯作者：
Hofmann, F
中科院分区：
文献类型：
--
作者：
Pfeifer, A;Klatt, P;Hofmann, F
平滑肌收缩调节是许多重要的生物学过程如组织灌注、心血管止血和胃肠运动所必需的。虽然钙的增加启动平滑肌收缩，但cGMP或cAMP可诱导平滑肌舒张，cGMP依赖性蛋白激酶I（cGKI）已被认为是这两种核苷酸舒张效应的主要介导物。以及其被cAMP交叉激活的假设，我们灭活了小鼠中编码cGKI的基因。cGKI的丧失破坏了平滑肌的一氧化氮（NO）/cGMP依赖性松弛，导致严重的血管和肠功能障碍。然而，cGKI缺陷的平滑肌对cAMP反应正常，表明cAMP和cGMP信号通过独立的途径，其中cGKI是小鼠平滑肌中NO/cGMP效应的特异性介导剂。
Regulation of smooth muscle contractility is essential for many important biological processes such as tissue perfusion, cardiovascular haemostasis and gastrointestinal motility, While an increase in calcium initiates smooth muscle contraction, relaxation can be induced by cGMP or cAMP, cGMP-dependent protein kinase I (cGKI) has been suggested as a major mediator of the relaxant effects of both nucleotides, To study the biological role of cGKT. and its postulated cross-activation by cAMP, we inactivated the gene coding for cGKI in mice. Loss of cGKI abolishes nitric oxide (NO)/cGMP-dependent relaxation of smooth muscle, resulting in severe vascular and intestinal dysfunctions, However, cGKI-deficient smooth muscle responded normally to cAMP, indicating that cAMP and cGMP signal via independent pathways, with cGKI being the specific mediator of the NO/cGMP effects in murine smooth muscle.