Parathyroid hormone inhibits proximal tubule Na(+)-K(+)-ATPase activity.
Parathyroid hormone (PTH) decreases the transepithelial transport of Na+ in the proximal tubule, an action ascribed to PTH-inhibited apical Na(+)-H+ exchanger-dependent Na+ entry. We tested the possibility that PTH could also diminish Na(+)-K(+)-ATPase-dependent Na+ exit. To dissociate effects on Na+ entry, studies were performed in a suspension of rat proximal tubules by measuring nystatin-stimulated ouabain-inhibitable O2 consumption (QO2) and monensin-stimulated ouabain-sensitive 86Rb uptake in the absence or presence of bovine PTH-(1-34) fragment. PTH inhibited the percent nystatin-stimulated QO2 in a concentration-dependent manner, with maximal effect at 10(-10) M. PTH-increased cAMP formation was seen at doses higher than 10(-9) M and was maximal at 10(-7) M. Dibutyryl cAMP (10(-4) M) only partially reproduced the PTH action on QO2. Angiotensin II (10(-6) M) blunted the effect of 10(-7) M PTH on QO2, although it did not change 10(-7) M PTH-dependent cAMP generation. The analogues PTH-(3-34) and [Nle8,Nle18,Tyr34]PTH-(3-34)-amide mimicked the effects of PTH-(1-34) on QO2 but did not affect cAMP formation. Monensin-stimulated ouabain-sensitive 86Rb uptake was inhibited by PTH in a dose-dependent manner, with 10(-7) M PTH being maximally inhibitory. Na(+)-K(+)-ATPase activity was also decreased by PTH-(3-34) in a concentration-dependent manner, with maximal effect occurring at 10(-8) M. Agonist-dependent inhibition of Na+ pump was not due to a decrease of mitochondrial activity, because mitochondrial uncoupled QO2 rates were the same in control and PTH-treated tubules.(ABSTRACT TRUNCATED AT 250 WORDS)
Ribeiro
C P
CP
Department of Cell Biology, Duke University, Durham, North Carolina 27710.
Mandel
L J
LJ
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D007687:Kidney Tubules, Proximal / Q000201:enzymology*; D008985:Monensin / Q000494:pharmacology; D009761:Nystatin / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D010101:Oxygen Consumption; D010281:Parathyroid Hormone / Q000494:pharmacology*; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D010281:Parathyroid Hormone; D000804:Angiotensin II; D009761:Nystatin; D010042:Ouabain; D003994:Bucladesine; D008985:Monensin; D000242:Cyclic AMP; D000254:Sodium-Potassium-Exchanging ATPase