体内G蛋白偶联受体的解偶联：来自转基因小鼠的见解。

Uncoupling of G-protein coupled receptors in vivo: insights from transgenic mice.

作者信息

Rockman H A

机构信息

Department of Medicine, University of California at San Diego, School of Medicine, La Jolla, USA.

出版信息

Adv Exp Med Biol. 1997;430:67-72. doi: 10.1007/978-1-4615-5959-7_6.

DOI:10.1007/978-1-4615-5959-7_6

PMID:9330719

Abstract

Heart failure is a problem of increasing importance in medicine. An important characteristic of heart failure is reduced agonist-stimulated adenylyl cyclase activity (receptor desensitization) due to both diminished receptor number (receptor down regulation) and impaired receptor function (receptor uncoupling). These changes in the beta-adrenergic receptor (beta-AR) system, may in part account for some of the abnormalities of contractile function in this disease. Myocardial contraction is closely regulated by G-protein coupled beta-adrenergic receptors through the action of the second messenger cAMP. The beta-AR receptors themselves are regulated by a set of specific kinases, termed the G-protein-coupled receptor kinases (GRKs). The study of this complex system in vivo has recently been advanced by the development of transgenic and gene targeted ("knockout") mouse models. Combining transgenic technology with sophisticated physiological measurements of cardiac hemodynamics is an extremely powerful strategy to study the regulation of myocardial contractility in the normal and failing heart.

摘要

心力衰竭在医学领域的重要性日益凸显。心力衰竭的一个重要特征是，由于受体数量减少（受体下调）和受体功能受损（受体解偶联），激动剂刺激的腺苷酸环化酶活性降低（受体脱敏）。β-肾上腺素能受体（β-AR）系统的这些变化，可能部分解释了该疾病中一些收缩功能异常的原因。心肌收缩通过第二信使环磷酸腺苷（cAMP）的作用，由G蛋白偶联β-肾上腺素能受体密切调节。β-AR受体本身受一组特定激酶的调节，这些激酶称为G蛋白偶联受体激酶（GRK）。最近，通过转基因和基因靶向（“敲除”）小鼠模型的开发，对该复杂系统的体内研究取得了进展。将转基因技术与复杂的心脏血流动力学生理测量相结合，是研究正常和衰竭心脏中心肌收缩力调节的极其有效的策略。