Madhun Z T, Ernsberger P, Ke F C, Zhou J, Hopfer U, Douglas J G
Department of Medicine, Case Western Reserve University, School of Medicine, Cleveland, OH 44106-4982.
Regul Pept. 1993 Mar 19;44(2):149-57. doi: 10.1016/0167-0115(93)90238-4.
Recent evidence suggests that there are two classes of receptors for angiotensin II (AngII), AT1 which is sensitive to losartan (DuP753) and is G-protein coupled, and AT2 which is sensitive to both PD123319 and CGP42112A, and is non-G-protein coupled. In rat mesangial cells two subtypes of AT1 receptor could be distinguished, AT1A subtype is more sensitive to losartan whereas AT1B subtype is more sensitive to PD123319, but insensitive to CGP42112A. The present studies were designed to ascertain which receptor subtype mediates three AngII-induced physiologic functions in rat mesangial cells namely intracellular Ca2+ mobilization, adenylyl cyclase inhibition and protein synthesis as monitored via [3H]leucine incorporation. The rank order of potency for inhibition of AngII-induced [Ca(2+)]i mobilization and adenylyl cyclase regulation was PD123319 > or = losartan > CGP42112A. By contrast, losartan was quite effective at inhibiting protein synthesis (IC50 = 8 nM) while PD123319 was without effect. These findings are consistent with AngII mediated signal transduction through AT1A and AT1B sites for phospholipase C mediated [Ca(2+)]i mobilization and inhibition of adenylyl cyclase. On the other hand, AT1A receptors appear to exclusively mediate AngII-induced protein synthesis. These observations underscore the complexity of AngII mediated signal transduction in glomerular mesangium.
最近有证据表明，血管紧张素II（AngII）存在两类受体，即对氯沙坦（DuP753）敏感且与G蛋白偶联的AT1受体，以及对PD123319和CGP42112A均敏感且不与G蛋白偶联的AT2受体。在大鼠系膜细胞中，可以区分出AT1受体的两种亚型，AT1A亚型对氯沙坦更敏感，而AT1B亚型对PD123319更敏感，但对CGP42112A不敏感。本研究旨在确定哪种受体亚型介导大鼠系膜细胞中AngII诱导的三种生理功能，即细胞内Ca2+动员、腺苷酸环化酶抑制和通过[3H]亮氨酸掺入监测的蛋白质合成。抑制AngII诱导的[Ca(2+)]i动员和腺苷酸环化酶调节的效力顺序为PD123319≥氯沙坦＞CGP42112A。相比之下，氯沙坦在抑制蛋白质合成方面相当有效（IC50 = 8 nM），而PD123319则无效。这些发现与AngII通过AT1A和AT1B位点介导信号转导以促进磷脂酶C介导[Ca(2+)]i动员和抑制腺苷酸环化酶一致。另一方面，AT1A受体似乎专门介导AngII诱导的蛋白质合成。这些观察结果强调了AngII在肾小球系膜中信号转导的复杂性。
