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 excha nger (NHE-3). We examined the mechanisms by which PTH inhibits NHE-3 activi ty by giving an acute intravenous PTD bolus to parathyroidectomized rats. P arathyroidectomy per se increased apical membrane NHE-3 activity and antige n. 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 accomp anied by increased NHE-3 phosphorylation. In contrast to the rapid changes in NHE-3 activity and phosphorylation, decrease in apical membrane NHE-3 an tigen 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 cor tical NHE-3 antigen. Pretreatment of the animals with the microtubule-disru pting agent colchicine blocked the PTH-induced decrease in apical NHE-3 ant igen. We propose that PTH acutely cause a decrease in NHE-3 intrinsic trans port activity possibly via a phosphorylation-dependent mechanism followed b y a decrease in apical membrane NHE-3 antigen via changes in protein traffi cking.