Potassium negatively regulates angiotensin II type 1 receptor expression in human adrenocortical H295R cells

Ian M. Bird, R. Ann Word, Colin Clyne, J. Ian Mason, William E. Rainey

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

We have previously shown that the human adrenocortical H295R cell line expresses the type I angiotensin II receptor (AT1-R) and that expression of this receptor is downregulated at the level of mRNA by forskolin or dibutyryl-cAMP as well as by angiotensin II (Ang II). In this study we examine the effects of K+ on both AT1-R mRNA and receptors, as monitored through 125I-Ang II binding in the presence of PD 123319. After treatment with a maximal stimulatory steroidogenic dose of K+ (14 mmol/L), H295R cells showed an increase in cytosolic free Ca2+ from 113 to 212 nmol/L. Unlike the effects of Ang II, this increase could be abolished by pretreatment with the Ca2+ channel antagonist nifedipine (1 μmol/L). AT1-R mRNA levels also fell in response to elevated extracellular K+ in a dose-dependent (K(d), 9 mmol/L; maximal fall in message at 12 mmol/L) and time-dependent (maximum 50%, at 12 hours) manner. The change in AT1-R mRNA level was less rapid than that in response to activation of phosphoinositidase C by Ang II or adenylyl cyclase by forskolin or by dibutyryl-cAMP. Unlike the action of Ang II but similar to the action of forskolin or dibutyryl-cAMP, the action of K+ was sustained. Changes in mRNA level in response to treatment with K+, Ang II, or dibutyryl-cAMP were also paralleled by changes in 125I-Ang II binding in each case. The mechanism of action of K+ on AT1-R mRNA also appears to be mediated through the opening of voltage-sensitive channels on the plasma membrane because the drop in AT1-R mRNA was similarly abolished by the Ca2+ channel blocker nifedipine. In conclusion, our findings show that AT1-R mRNA levels can be controlled through a Ca2+-dependent signaling pathway, as well as through phosphoinositidase C or adenylyl cyclase signaling pathways, and that these changes in mRNA level underlie a corresponding change in receptor protein at the cell surface.

Original languageEnglish (US)
Pages (from-to)1129-1134
Number of pages6
JournalHypertension
Volume25
Issue number6
DOIs
StatePublished - Jun 1995

Keywords

  • adrenal
  • angiotensin II
  • calcium
  • human
  • potassium
  • receptor

ASJC Scopus subject areas

  • Internal Medicine

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