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

Am J Physiol. 1999 May;276(5):F711-9. doi: 10.1152/ajprenal.1999.276.5.F711.

Abstract

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 phospholipase A2 (PLA2), or [Nle8,18,Tyr34]PTH-(3-34) (10 U), which couples to PLC and PLA2 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 3-fold, urine output (V) 2.0 +/- 0.1-fold, and lithium clearance (CLi) 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%. [Nle8,18,Tyr34]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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Biological Transport / drug effects
  • Carrier Proteins / metabolism*
  • Cyclic AMP / urine
  • Enzyme Activation / drug effects
  • Kidney / chemistry
  • Kidney / drug effects
  • Kidney / enzymology
  • Lithium / urine
  • Male
  • Parathyroid Hormone / pharmacology
  • Peptide Fragments / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects
  • Sodium / metabolism
  • Sodium-Hydrogen Exchanger 3
  • Sodium-Hydrogen Exchangers / metabolism*
  • Sodium-Phosphate Cotransporter Proteins
  • Sodium-Potassium-Exchanging ATPase / metabolism*
  • Symporters*
  • Teriparatide / analogs & derivatives*
  • Teriparatide / pharmacology
  • Urine

Substances

  • Carrier Proteins
  • Parathyroid Hormone
  • Peptide Fragments
  • Slc9a3 protein, rat
  • Sodium-Hydrogen Exchanger 3
  • Sodium-Hydrogen Exchangers
  • Sodium-Phosphate Cotransporter Proteins
  • Symporters
  • Teriparatide
  • parathyroid hormone (1-34)amide, Nle(8), Nle(18), Tyr(34)-
  • Lithium
  • Sodium
  • Cyclic AMP
  • Sodium-Potassium-Exchanging ATPase