The new pathophysiological role and its mechanism of angiotensin receptor

为探讨血管紧张素1型受体（AT 1 R）和血管紧张素2型受体（AT 2 R）在肾上皮细胞系MDCKII和嗜铬细胞瘤细胞系PC-12中的新的病理生理作用及其机制，我们采用MDCKII细胞和PC-12细胞作为实验材料。在稳定转染大鼠AT 2 R的MDCKII细胞中，血管紧张素II（Ang II）刺激抑制forskolin诱导的cAMP积累，并呈剂量依赖性。这种抑制作用可被AT 2 R拮抗剂PD 123319或百日咳毒素预处理所消除，表明AT 2 R刺激的Gi蛋白偶联机制被阻断。在AT 1 R拮抗剂处理下，用Ang II刺激该细胞激活细胞外信号调节激酶（ERK）1/2的磷酸化。在瞬时表达大鼠AT 1 R的PC-12细胞中，Ang Ⅱ降低AT 2 R的mRNA和蛋白水平。AT 1AR和AT 2 R双转染PC-12细胞可诱导Ang Ⅱ诱导的AT 2 R内化。结果提示：1）AT 2 R通过Gi蛋白偶联途径激活ERK 1/2而影响细胞生长; 2）AT 1 R通过某种未知的途径影响AT 2 R的表达。基于这些结果，应需要进一步的研究，使用整个动物，以澄清AT 2 R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.