Potassium Negatively Regulates Angiotensin II Type 1 Receptor Expression in Human Adrenocortical H295R Cells

• Published in: Hypertension (Dallas, Tex. 1979) Tex. 1979), 1995-06, Vol.25 (6), p.1129-1134
• Main Authors: Bird, Ian M, Word, R. Ann, Clyne, Colin J, Mason, Ian, Rainey, William E
• Format: Article
• Language: English
• Subjects: Adrenal Cortex - metabolism; Adrenals. Interrenals; Adrenocortical hormones. Regulation; Angiotensin II - metabolism; Biological and medical sciences; Calcium - metabolism; Cell Line; Colforsin - pharmacology; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation - drug effects; Humans; Nifedipine - pharmacology; Potassium - pharmacology; Receptors, Angiotensin - genetics; RNA, Messenger - analysis; Vertebrates: endocrinology
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/01.hyp.25.6.1129

We have previously shown that the human adrenocortical H295R cell line expresses the type 1 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 Potassium on both AT (1) -R mRNA and receptors, as monitored through Iodine-Ang II binding in the presence of PD 123319. After treatment with a maximal stimulatory steroidogenic dose of Potassium (14 mmol/L), H295R cells showed an increase in cytosolic free Calcium from 113 to 212 nmol/L. Unlike the effects of Ang II, this increase could be abolished by pretreatment with the Calcium channel antagonist nifedipine (1 micro mol/L). AT1 -R mRNA levels also fell in response to elevated extracellular Potassium in a dose-dependent (Kd, 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 Potassium was sustained. Changes in mRNA level in response to treatment with Potassium (), Ang II, or dibutyryl-cAMP were also paralleled by changes in Iodine-Ang II binding in each case. The mechanism of action of Potassium 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 Calcium channel blocker nifedipine. In conclusion, our findings show that AT (1) -R mRNA levels can be controlled through a Calcium -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. (Hypertension. 1995;25:1129-1134.)