Type 1 Angiotensin receptor (AT1-R)-mediated decrease in type 2 Angiotensin receptor mRNA Level is dependent on G q and extracellular signal-regulated kinase 1/2 in at1-r-transfected PC12 cells

Masaki Saito, Y. Shinohara, H. Sasaki, Y. Netsu, M. Yoshida, Norimichi Nakahata

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

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, Gq inhibitor YM254980, and mitogen-activated protein kinase (MAPK) kinase 1/2 inhibitor U0126, but not by pertussis toxin, which uncouples the receptor with Gi, or p38 MAPK inhibitor SB203580. We suggest, possibly for the first time, that the hAT1-R/Gq/extracellular signal-regulated kinase 1/2 pathway is involved in the down-regulation of AT2-R using PC12 cells transfected with AT1-R.

Original languageEnglish
Pages (from-to)299-308
Number of pages10
JournalJournal of Neuroendocrinology
Volume20
Issue number3
DOIs
Publication statusPublished - 2008 Mar 1

Keywords

  • Extracellular signal-regulated kinase 1/2
  • PC12 cells
  • Type 1 angiotensin II receptor
  • Type 2 angiotensin receptor
  • mRNA expression

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Cellular and Molecular Neuroscience

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