Miura Shin-ichiro, Saku Keijiro, Karnik Sadashiva S
Department of Cardiology, Fukuoka University School of Medicine, Fukuoka, Japan.
Hypertens Res. 2003 Dec;26(12):937-43. doi: 10.1291/hypres.26.937.
The renin-angiotensin system hormone angiotensin II (Ang II) plays a central role in the pathophysiology of hypertension, cardiac hypertrophy, congestive heart failure, and coronary heart disease. Two distinct subtypes of Ang II receptor, type 1 (AT1) and type 2 (AT2), have been identified, and both have been shown to belong to the G-protein-coupled receptor superfamily (GPCRs). The recent Human Genome Project has revealed more than 1,000 transmembrane (TM) receptors that belong to this superfamily, and it has been estimated that 50% of all clinically used medicines modulate GPCRs activity. Recently, there have been many new insights regarding Ang II receptors and other GPCRs, such as on homo- and hetero-oligomerization, constitutive activation, movement of TM helices, internalization, desensitization and phosphorylation, trafficking, nuclear localization, intracellular protein-induced receptor activation, and receptor-associated proteins. Although AT1 receptor antagonists which prevent Ang II-induced signaling are already clinically available, we here summarize new findings regarding their structure and function, and the possibility of new therapeutic strategies for targeting Ang II receptors through molecular biological techniques.
肾素-血管紧张素系统激素血管紧张素II（Ang II）在高血压、心脏肥大、充血性心力衰竭和冠心病的病理生理学中起核心作用。已鉴定出两种不同的Ang II受体亚型，即1型（AT1）和2型（AT2），且二者均已被证明属于G蛋白偶联受体超家族（GPCRs）。最近的人类基因组计划已揭示出1000多种属于该超家族的跨膜（TM）受体，据估计，所有临床使用的药物中有50%可调节GPCRs的活性。最近，关于Ang II受体和其他GPCRs有许多新的见解，例如关于同源和异源寡聚化、组成性激活、TM螺旋运动、内化、脱敏和磷酸化、运输、核定位、细胞内蛋白诱导的受体激活以及受体相关蛋白等方面。尽管已在临床上使用可阻止Ang II诱导信号传导的AT1受体拮抗剂，但我们在此总结关于其结构和功能的新发现，以及通过分子生物学技术靶向Ang II受体的新治疗策略的可能性。
