Hata Jonathan A, Koch Walter J
Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
Mol Interv. 2003 Aug;3(5):264-72. doi: 10.1124/mi.3.5.264.
In the heart, beta -adrenergic receptors (beta ARs), members of the superfamily of G protein-coupled receptors (GPCRs), modulate cardiac responses to catecholamines. beta AR signaling, which is compromised in many cardiac diseases (e.g., congestive heart failure), is regulated by GPCR kinases (GRKs). Levels of the most abundant cardiac GRK, known as GRK2 or beta AR kinase 1 (beta ARK1), are increased in both animal and human heart failure. Transgenic mouse models have demonstrated that beta ARK1 plays a vital role in cardiac function and development, as well as in the regulation of myocardial signaling, and pharmacological studies have further implicated GRKs in the impairment of cardiac GPCR signaling. Gene therapy, along with the development of small-molecule modulators of GRK activity, has indicated in multiple animal models that the manipulation of GRK activity may elicit therapeutic benefits in many forms of cardiac disease.
在心脏中，β-肾上腺素能受体（βARs）是G蛋白偶联受体（GPCRs）超家族的成员，可调节心脏对儿茶酚胺的反应。βAR信号传导在许多心脏疾病（如充血性心力衰竭）中受损，它受GPCR激酶（GRKs）调节。在动物和人类心力衰竭中，最丰富的心脏GRK即GRK2或β-肾上腺素能受体激酶1（βARK1）的水平都会升高。转基因小鼠模型已证明βARK1在心脏功能和发育以及心肌信号调节中起着至关重要的作用，药理学研究进一步表明GRKs与心脏GPCR信号传导受损有关。基因治疗以及GRK活性小分子调节剂的开发，已在多个动物模型中表明，对GRK活性的调控可能会在多种形式的心脏疾病中产生治疗益处。
