期刊
JOURNAL OF NEUROENDOCRINOLOGY
卷 20, 期 3, 页码 299-308出版社
WILEY
DOI: 10.1111/j.1365-2826.2008.01646.x
关键词
extracellular signal-regulated kinase 1/2; mRNA expression; PC12 cells; type 1 angiotensin II receptor; type 2 angiotensin receptor
Angiotensin II (Ang II) functions through two major Ang II receptor subtypes, type 1 (AT1-R) and type 2 (AT2-R), both of which are classified to be G protein-coupled receptors. AT2-R is highly expressed at the fetal stage, and in heart remodelling and brain ischaemia; therefore, it is important to clarify the regulatory mechanisms of AT2-R expression. Although AT1-R is generally believed to modulate AT2-R expression in some tissues or cells, the exact mechanism remains to be clarified. In the present study, we examined the effect of AT1-R stimulation on expression of endogenous rat AT2-R (rAT2-R) in AT1-R-transfected PC12 cells. rAT2-R mRNA and protein expression were decreased by Ang II in PC12 cells transfected with rAT1A-R in a time-dependent manner, mediated through a decline in mRNA stability. The C-terminus of G protein-coupled receptor (GPCR) is important for GPCR-mediated signal transduction. Therefore, we used C-terminus-deleted human AT1-R (hAT1-327STOP), which is thought to be a nondesensitised mutant of hAT1-R. As a result, Ang II decreased rAT2-R mRNA expression to a greater extent in cells transfected with hAT1-327STOP than with wild-type hAT1-R. The decrease was completely reversed by AT1-R antagonist candesartan, G(q) inhibitor YM254980, and mitogen-activated protein kinase (MAPK) kinase 1/2 inhibitor U0126, but not by pertussis toxin, which uncouples the receptor with G(i), or p38 MAPK inhibitor SB203580. We suggest, possibly for the first time, that the hAT1-R/G(q)/extracellular signal-regulated kinase 1/2 pathway is involved in the down-regulation of AT2-R using PC12 cells transfected with AT1-R.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据