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 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.
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002352:Carrier Proteins / Q000378:metabolism*; D000242:Cyclic AMP / Q000652:urine; D004789:Enzyme Activation / Q000187:drug effects; D007668:Kidney / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology; D008094:Lithium / Q000652:urine; D008297:Male; D010281:Parathyroid Hormone / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D012964:Sodium / Q000378:metabolism; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*; D050608:Sodium-Phosphate Cotransporter Proteins; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D027981:Symporters; D019379:Teriparatide / Q000031:analogs & derivatives* / Q000494:pharmacology; D014556:Urine