Potassium negatively regulates angiotensin II type 1 receptor expression in human adrenocortical H295R cells.
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 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 mumol/L). AT1-R mRNA levels also fell in response to elevated extracellular K+ 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 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Bird
I M
IM
Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas 75235-9032, USA.
Word
R A
RA
Clyne
C
C
Mason
J I
JI
Rainey
W E
WE
D000302:Adrenal Cortex / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D009543:Nifedipine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis*; D011945:Receptors, Angiotensin / Q000235:genetics*
D012333:RNA, Messenger; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D005576:Colforsin; D009543:Nifedipine; D011188:Potassium; D002118:Calcium