The new pathophysiological role and its mechanism of angiotensin receptor

为了探讨血管紧张素1型受体(AT1R)和血管紧张素2型受体(AT2R)的新的病理生理作用及其机制，我们使用了肾上皮细胞系MDCKII和嗜铬细胞瘤细胞PC-12。在稳定表达AT2R的MDCKII细胞中，血管紧张素II(Ang II)可剂量依赖性地抑制Forsklin诱导的环磷酸腺苷(CAMP)积聚。这种抑制作用可被AT2R拮抗剂PD123319或百日咳毒素预先处理所消除，这表明AT2R刺激的Gi蛋白偶联机制被激活。AT1R拮抗剂Ang II刺激PC-12细胞后，激活了细胞外信号调节激酶(ERK)1/2的磷酸化。Ang II降低了瞬时表达大鼠AT1R的PC-12细胞AT2R的mRNA和蛋白水平。血管紧张素Ⅱ诱导PC-12细胞AT1AR和AT2R内化。这些结果提示：1)AT2R通过GI蛋白偶联机制激活ERK1/2影响细胞生长；2)AT1R通过某种未知机制影响AT2R的表达。基于这些结果，需要对整个动物进行进一步的研究，以阐明AT2R的病理生理作用。

To investigate the new pathophysiological role and its mechanisms of angiotensin type 1 receptor (AT1R) and angiotensin type 2 receptor (AT2R), we used MDCKII cell, a renal epithelial cell line, and PC-12 cell, a pheochromocytoma cell. In MDCKII cell stably transfected with rat AT2R, the stimulation with angiotensin II (Ang II) inhibited forskolin-induced cyclic AMP accumulation with dose-dependent manner. This inhibition was abolished by co-treatment with PD123319, a AT2R antagonist, or pre-treatment of pertussis toxin, suggesting the perticipation of the Gi protein-coupled mechanism of AT2R stimulation. The stimulation of this cell with Ang II under treatment AT1R antagonist activated the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2. Ang II reduced mRNA and protein level of AT2R in PC-12 cells transiently expressed rat AT1R. Double transfection of AT1AR and AT2R on PC-12 cells induced the Ang II-induced internalization of AT2R. These results suggest that 1) AT2R affect cell growth through activation of ERK 1/2 with Gi protein-coupled mechanism, 2) AT1R affect the AT2R expression with some unknown mechanism. Based on these results, further investigations using whole animal should be needed for clarify the pathophysiological role of AT2R.