Regulation of rat renal alpha 2 B-adrenergic receptors by potassium depletion.
Potassium depletion and alpha 2-adrenergic receptor (alpha 2-AR) agonists produce similar physiological effects on renal function. Both stimuli increase Na-H exchange in proximal tubule cells, inhibit water transport in collecting tubule cells, and alter blood pressure regulation. The purpose of this study was to determine whether potassium depletion and renal alpha 2-AR subtype expression were linked. Kidney membrane proteins and RNA were harvested from anesthetized rats fed a potassium-deficient diet for 4-20 days (LK 4 to LK 20). Using a selective alpha 2-AR antagonist, [3H]MK-912, we observed that potassium depletion led to a dramatic increase in maximum binding (270% of control) without a change in dissociation constant. Competitive binding studies in LK 14 kidney membranes employing chlorpromazine, prazosin, and oxymetazoline suggested that the increase in alpha 2-ARs in response to potassium depletion was due primarily to an increase in the B subtype of alpha 2-AR. Northern blot analysis demonstrated that renal alpha 2B-AR mRNA levels increased (190% of control) after 4 or 14 days on a potassium-deficient diet. In contrast, there was no difference in steady-state alpha 2A-receptor protein levels by Western blot analysis. We conclude that potassium depletion selectively increases the expression of the B subtype of alpha 2-AR with no detectable effect on alpha 2A-AR expression.
Muir
J C
JC
Department of Medicine, University of Virginia Health Sciences Center, Charlottesville 22908.
Huang
L
L
Harrison
J K
JK
Rosin
D L
DL
Okusa
M D
MD
D000317:Adrenergic alpha-Antagonists / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D015152:Blotting, Northern; D015153:Blotting, Western; D002462:Cell Membrane / Q000378:metabolism; D015870:Gene Expression; D007668:Kidney / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D011191:Potassium Deficiency / Q000378:metabolism*; D011807:Quinolizines / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000302:isolation & purification; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D014316:Tritium; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D011807:Quinolizines; D012333:RNA, Messenger; D018341:Receptors, Adrenergic, alpha-2; D014316:Tritium; C054290:L 657743; D015016:Yohimbine