cGMP 激酶 I 缺陷小鼠中平滑肌调节功能缺陷
Defective smooth muscle regulation in cGMP kinase I-deficient mice.
作者信息
Pfeifer A, Klatt P, Massberg S, Ny L, Sausbier M, Hirneiss C, Wang G X, Korth M, Aszódi A, Andersson K E, Krombach F, Mayerhofer A, Ruth P, Fässler R, Hofmann F
机构信息
Institut für Pharmakologie und Toxikologie, München, Biedersteiner, Str. 29, 80802 Müchen, Germany.
出版信息
EMBO J. 1998 Jun 1;17(11):3045-51. doi: 10.1093/emboj/17.11.3045.
Abstract
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 cGKI 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.
摘要
平滑肌收缩性的调节对于许多重要的生物学过程至关重要，如组织灌注、心血管止血和胃肠蠕动。虽然钙的增加会引发平滑肌收缩，但cGMP或cAMP可诱导其舒张。cGMP依赖性蛋白激酶I（cGKI）被认为是这两种核苷酸舒张作用的主要介质。为了研究cGKI的生物学作用及其假定的被cAMP交叉激活的情况，我们使小鼠中编码cGKI的基因失活。cGKI的缺失消除了一氧化氮（NO）/cGMP依赖性的平滑肌舒张，导致严重的血管和肠道功能障碍。然而，cGKI缺陷的平滑肌对cAMP反应正常，表明cAMP和cGMP通过独立途径发出信号，cGKI是小鼠平滑肌中NO/cGMP效应的特异性介质。
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