Type 1 angiotensin receptor (AT1-R)-mediated decrease in type 2 angiotensin receptor mRNA level is dependent on Gq and extracellular signal-regulated kinase 1//2 in AT1-R-transfected PC12 cells

Journal of Neuroendocrinology
M SaitoN Nakahata

Abstract

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...Continue Reading

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Citations

Oct 16, 2009·American Journal of Physiology. Cell Physiology·Sarvesh JajooVickram Ramkumar
Apr 25, 2012·Journal of the Renin-angiotensin-aldosterone System : JRAAS·Juan GaoLie Gao
Oct 29, 2009·Journal of the Renin-angiotensin-aldosterone System : JRAAS·Helmy M Siragy

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