Abstract：
G protein-coupled receptors (GPCRs) mediate cellular responses to a myriad of hormones and neurotransmitters that play vital roles in the regulation of physiological processes such as blood pressure. In organs such as the artery and kidney, hormones or neurotransmitters, such as angiotensin II (Ang II), dopamine, epinephrine, and norepinephrine exert their functions via their receptors, with the ultimate effect of keeping normal vascular reactivity, normal body sodium, and normal blood pressure. GPCR kinases (GRKs) exert their biological functions, by mediating the regulation of agonist-occupied GPCRs, non-GPCRs, or non-receptor substrates. In particular, increasing number of studies show that aberrant expression and activity of GRKs in the cardiovascular system and kidney inhibit or stimulate GPCRs (e.g., dopamine receptors, Ang II receptors, and α- and β-adrenergic receptors), resulting in hypertension. Current studies focus on the effect of selective GRK inhibitors in cardiovascular diseases, including hypertension. Moreover, genetic studies show that GRK gene variants are associated with essential hypertension, blood pressure response to antihypertensive medicines, and adverse cardiovascular outcomes of antihypertensive treatment. In this review, we present a comprehensive overview of GRK-mediated regulation of blood pressure, role of GRKs in the pathogenesis of hypertension, and highlight potential strategies for the treatment of hypertension. Schematic representation of GPCR desensitization process. Activation of GPCRs begins with the binding of an agonist to its corresponding receptor. Then G proteins activate downstream effectors that are mediated by various signaling pathways. GPCR signaling is halted by GRK-mediated receptor phosphorylation, which causes receptor internalization through β-arrestin.
摘要：
G蛋白偶联受体（GPCRs）介导细胞对无数激素和神经递质的反应，这些激素和神经递质在调节血压等生理过程中起着至关重要的作用。在动脉和肾脏等器官中，激素或神经递质，例如血管紧张素II（AngII），多巴胺,肾上腺素,去甲肾上腺素通过它们的受体发挥它们的功能，最终的效果是保持正常的血管反应性，正常的身体钠，和正常的血压。GPCR激酶（GRKs）发挥其生物学功能，通过介导激动剂占据的GPCRs的调节，非GPCRs,或非受体底物。特别是,越来越多的研究表明，心血管系统和肾脏中GRKs的异常表达和活性抑制或刺激GPCRs(例如，多巴胺受体,AngII受体,和α-和β-肾上腺素能受体），导致高血压。目前的研究集中在选择性GRK抑制剂在心血管疾病中的作用。包括高血压.此外，基因研究表明GRK基因变异与原发性高血压,降压药物对血压的反应，和抗高血压治疗的不良心血管结局。在这次审查中,我们对GRK介导的血压调节进行了全面的概述，GRKs在高血压发病机制中的作用,并强调治疗高血压的潜在策略。GPCR脱敏过程的示意图。GPCR的激活始于激动剂与其相应受体的结合。然后G蛋白激活由各种信号通路介导的下游效应子。GPCR信号通过GRK介导的受体磷酸化停止，通过β抑制蛋白引起受体内化。
