PARATHYROID-HORMONE INHIBITS PROXIMAL TUBULE NA+-K+-ATPASE ACTIVITY

被引:50
作者
RIBEIRO, CP
MANDEL, LJ
机构
来源
AMERICAN JOURNAL OF PHYSIOLOGY | 1992年 / 262卷 / 02期
关键词
SODIUM-POTASSIUM-ADENOSINE-TRIPHOSPHATASE; ADENOSINE; 3'; 5'-CYCLIC MONOPHOSPHATE; PROTEIN KINASE-A; ANGIOTENSIN-II;
D O I
10.1152/ajprenal.1992.262.2.F209
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
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 Rb-86 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 Rb-86 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. We conclude that PTH inhibits the proximal tubule Na+-K+-ATPase, an action which appears to be dissociated from cAMP generation.
引用
收藏
页码:F209 / F216
页数:8
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