In vivo PTH provokes apical NHE3 and NaPi2 redistribution and Na-K-ATPase inhibition

The aim of this study was to test the hypothesis that in vivo administration of parathyroid hormone (PTH) provokes diuresis/natriuresis through redistribution of proximal tubule apical sodium cotransporters (NHE3 and NaPi2) to internal stores and inhibition of basolateral Na-K-ATPase activity and to determine whether the same cellular signals drive the changes in apical and basolateral transporters. PTH-(1-34) (20 U), which couples to adenylate cyclase (AC), phospholipase C (PLC), and phospholipaseA(2) (PLA(2)), or [Nle(8,18),Tyr(34)]PTH-(3- 34) (10 U), which couples to PLC and PLA(2) but not AC, were given to anesthetized rats as an intravenous bolus followed by low-dose infusion (1 U.kg(-1).min(-1) for 1 h). Renal cortex membranes were fractionated on sorbitol density gradients. PTH-(1-34) increased urinary cAMP excretion S-fold, urine output (V) 2.0 +/- 0.1-fold, and lithium clearance (C(Li)) 2.8 +/- 0.3-fold. With this diuresis/natriuresis, 25% of NHE3 and 18% of NaPi2 immunoreactivity redistributed from apical membranes to higher density fractions containing intracellular membrane markers, and basolateral Na-K-ATPase activity decreased 25%. [Nle(8,18),Tyr(34)]PTH-(3-34) failed to increase V or CLi Or to provoke redistribution of NHE3 or NaPi2, but it did inhibit Na-K-ATPase activity 25%. We conclude that in vivo PTH stimulates natriuresis/diuresis associated with internalization of apical NHE3 and NaPi2 and inhibition of Na-K-ATPase activity, that cAMP-protein kinase A stimulation is necessary for the natriuresis/diuresis and NHE3 and NaPi2 internalization, and that Na-K-ATPase inhibition is not secondary to depressed apical Na(+) transport.