Harris C A, Chuang T T, Scorer C A
Department of Molecular Recognition, GlaxoSmithKline Medicines Research Centre, Stevenage, Hertfordshire, UK.
Basic Res Cardiol. 2001 Jul;96(4):364-8. doi: 10.1007/s003950170044.
Reduced beta-adrenergic responsiveness in the heart is a characteristic feature of heart failure. G protein-coupled receptor kinase 2 (GRK2) phosphorylates beta-adrenoceptors in an agonist-dependent manner, causing receptor uncoupling and desensitisation. Elevated levels of both GRK2 mRNA and activity have been shown to occur in the failing human heart (Ungerer et al. (1992) Circulation 87: 454-463). We have analysed levels of GRK2 protein in heart tissue from the cardiomyopathic Syrian hamster CHF 147 and compared these to GRK2 levels in age-matched, non-cardiomyopathic control hamsters (CHF 148). GRK2 protein levels were found to be significantly increased in the left ventricles of the cardiomyopathic hamsters compared to the controls. The relative amounts of GRK2 in the cardiomyopathic hamsters, as compared to normal controls, increased with age from 2-fold at 100 days to 5-fold at 350 days. These animals should provide a useful model for testing the effect of GRK2 inhibitors on the development of heart failure.
心脏中β-肾上腺素能反应性降低是心力衰竭的一个特征。G蛋白偶联受体激酶2（GRK2）以激动剂依赖的方式使β-肾上腺素能受体磷酸化，导致受体解偶联和脱敏。在衰竭的人类心脏中已显示GRK2 mRNA水平和活性均升高（Ungerer等人，（1992年）《循环》87：454 - 463）。我们分析了心肌病叙利亚仓鼠CHF 147心脏组织中GRK2蛋白的水平，并将其与年龄匹配的非心肌病对照仓鼠（CHF 148）中的GRK2水平进行比较。发现与对照组相比，心肌病仓鼠左心室中的GRK2蛋白水平显著升高。与正常对照相比，心肌病仓鼠中GRK2的相对量随年龄增加，从100天时的2倍增加到350天时的5倍。这些动物应该为测试GRK2抑制剂对心力衰竭发展的影响提供一个有用的模型。
