Dual mechanisms of regulation of Na/H exchanger NHE-3 by parathyroid hormone in rat kidney.
Parathyroid hormone (PTH) is a potent inhibitor of mammalian renal proximal tubule sodium absorption via suppression of the apical membrane Na/H exchanger (NHE-3). We examined the mechanisms by which PTH inhibits NHE-3 activity by giving an acute intravenous PTH bolus to parathyroidectomized rats. Parathyroidectomy per se increased apical membrane NHE-3 activity and antigen. Acute infusion of PTH caused a time-dependent decrease in NHE-3 activity as early as 30 min. Decrease in NHE-3 activity at 30 and 60 min was accompanied by increased NHE-3 phosphorylation. In contrast to the rapid changes in NHE-3 activity and phosphorylation, decrease in apical membrane NHE-3 antigen was not detectable until 4-12 h after the PTH bolus. The decrease in apical membrane NHE-3 occurred in the absence of changes in total renal cortical NHE-3 antigen. Pretreatment of the animals with the microtubule-disrupting agent colchicine blocked the PTH-induced decrease in apical NHE-3 antigen. We propose that PTH acutely cause a decrease in NHE-3 intrinsic transport activity possibly via a phosphorylation-dependent mechanism followed by a decrease in apical membrane NHE-3 antigen via changes in protein trafficking.
Fan
L
L
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75225-8856, USA.
Wiederkehr
M R
MR
Collazo
R
R
Wang
H
H
Crowder
L A
LA
Moe
O W
OW
D000595:Amino Acid Sequence; D000818:Animals; D003078:Colchicine / Q000494:pharmacology; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism*; D008969:Molecular Sequence Data; D010281:Parathyroid Hormone / Q000378:metabolism*; D016105:Parathyroidectomy; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000276:immunology / Q000378:metabolism*
D010281:Parathyroid Hormone; C000613387:Slc9a3 protein, rat; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D003078:Colchicine