Matsubara H, Mori Y, Masaki H, Inada M
Nihon Rinsho. 1998 Jul;56(7):1912-8.
Angiotensin II (Ang II) receptors are classified into two subtypes, type 1 (ATF-R) and type 2 (AT2-R) by development of non-peptidic antagonists. Classical Ang II function including vasopressor effect, cardiotropic action and aldosterone production is mainly mediated through AT1-R that present in cardiovascular system, adrenal glands and kidneys. AT1-R is abundantly expressed in whole bodies of fetus and its expression is abruptly decreased after birth, and in the adult AT2-R is expressed in brain nuclei, uterus, adrenal medullary glands and ovary. AT1-R and AT2-R are both G-protein coupled receptors and have 46% similarity in amino acid levels with seventh transmembrane conformation. Signal transduction pathway of AT1-R is mainly CA2+ and activation of protein kinase C, while that of AT2-R is still unknown. Clinical application of AT1-R antagonist started and this causes elevation of plasma Ang II levels, which selectively stimulates AT2-R. Thus, one should realize AT2-R-mediated effect in treatment with AT1-R antagonist. We have shown that AT2-R has anti-AT1-R action, such as inhibitory action against AT1-R-mediated positive chronotropic effect or AT1-R-induced proliferative effect, resulting in the protective effects on Ang II-induced cardiovasucular and renal action. Thus, elucidation of AT2-R function will be important in clinical treatment with AT1-R antagonists.
通过非肽类拮抗剂的研发，血管紧张素II（Ang II）受体被分为两种亚型，即1型（AT1-R）和2型（AT2-R）。包括升压作用、对心脏的作用及醛固酮分泌等经典的Ang II功能主要通过存在于心血管系统、肾上腺和肾脏中的AT1-R介导。AT1-R在胎儿全身大量表达，出生后其表达急剧下降，而在成体中，AT2-R在脑核、子宫、肾上腺髓质和卵巢中表达。AT1-R和AT2-R均为G蛋白偶联受体，在氨基酸水平上具有46%的相似性，均具有七次跨膜结构。AT1-R的信号转导途径主要是Ca2+和蛋白激酶C的激活，而AT2-R的信号转导途径尚不清楚。AT1-R拮抗剂的临床应用开始后，这导致血浆Ang II水平升高，后者选择性地刺激AT2-R。因此，在使用AT1-R拮抗剂治疗时应认识到AT2-R介导的效应。我们已经表明，AT2-R具有抗AT1-R作用，如对AT1-R介导的正性变时作用或AT1-R诱导的增殖作用的抑制作用，从而对Ang II诱导的心血管和肾脏作用产生保护作用。因此，阐明AT2-R的功能在AT1-R拮抗剂的临床治疗中具有重要意义。
