Ribeiro C P, Mandel L J
Department of Cell Biology, Duke University, Durham, North Carolina 27710.
Am J Physiol. 1992 Feb;262(2 Pt 2):F209-16. doi: 10.1152/ajprenal.1992.262.2.F209.
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)
甲状旁腺激素（PTH）可降低近端小管中Na⁺的跨上皮转运，这一作用归因于PTH抑制顶端Na⁺-H⁺交换体依赖性的Na⁺内流。我们测试了PTH是否也能减少Na⁺-K⁺-ATP酶依赖性的Na⁺外流。为了区分对Na⁺内流的影响，我们通过测量制霉菌素刺激的哇巴因抑制性O₂消耗（QO₂）以及在有无牛PTH-（1-34）片段存在的情况下莫能菌素刺激的哇巴因敏感性⁸⁶Rb摄取，在大鼠近端小管悬浮液中进行了研究。PTH以浓度依赖性方式抑制制霉菌素刺激的QO₂百分比，在10⁻¹⁰M时达到最大效应。在高于10⁻⁹M的剂量下可观察到PTH诱导的cAMP形成增加，在10⁻⁷M时达到最大。二丁酰cAMP（10⁻⁴M）仅部分重现了PTH对QO₂的作用。血管紧张素II（10⁻⁶M）减弱了10⁻⁷M PTH对QO₂的作用，尽管它并未改变10⁻⁷M PTH依赖性的cAMP生成。类似物PTH-（3-34）和[Nle8，Nle18，Tyr34]PTH-（3-34）-酰胺模拟了PTH-（1-34）对QO₂的作用，但不影响cAMP形成。莫能菌素刺激的哇巴因敏感性⁸⁶Rb摄取被PTH以剂量依赖性方式抑制，10⁻⁷M PTH具有最大抑制作用。PTH-（3-34）也以浓度依赖性方式降低Na⁺-K⁺-ATP酶活性，在10⁻⁸M时达到最大效应。激动剂依赖性的Na⁺泵抑制并非由于线粒体活性降低，因为对照和PTH处理的小管中线粒体解偶联的QO₂速率相同。（摘要截断于250字）
