Rodriguez-Commes J, Forrest J N, Lopez R, Gasalla-Herraiz J, Isales C M
Department of Medicine, Yale University School of Medicine, New Haven, CT, USA.
Biochem Biophys Res Commun. 1995 Aug 15;213(2):688-98. doi: 10.1006/bbrc.1995.2186.
The effects of parathyroid hormone (PTH) on sodium homeostasis in the distal tubule are not well defined. Using A6 cells as a model for distal tubular epithelium we measured equivalent short circuit current (leq), as an estimate of net sodium transport. We found that PTH increased leq in a dose-dependent manner. DDA, an agent which inhibits adenylate cyclase, decreased PTH-activated sodium transport, suggesting a role for cAMP elevation in PTH effects. Moreover, addition of Rp-cAMP, an inhibitor of cAMP-dependent protein kinase, partially blocked the PTH-stimulated leq. PTH also elicited a sustained increase in [Ca2+]i in A6 cells. This elevation in [Ca2+]i was abolished by removal of calcium from the extracellular medium, suggesting the involvement of calcium influx pathways. In fact, addition of the calcium channel blocker nitrendipine to PTH-stimulated leq partially blocked PTH-activated sodium transport. Taken together these data demonstrate that PTH stimulates electrogenic sodium transport in A6 cells and that this effect may be mediated through a rise in both intracellular calcium and cellular cAMP.
甲状旁腺激素（PTH）对远端肾小管钠稳态的影响尚未明确界定。我们使用A6细胞作为远端肾小管上皮的模型，测量等效短路电流（leq），作为净钠转运的估计值。我们发现PTH以剂量依赖的方式增加leq。DDA是一种抑制腺苷酸环化酶的试剂，它降低了PTH激活的钠转运，这表明cAMP升高在PTH作用中发挥作用。此外，添加cAMP依赖性蛋白激酶的抑制剂Rp-cAMP可部分阻断PTH刺激的leq。PTH还引起A6细胞中[Ca2+]i的持续增加。从细胞外培养基中去除钙可消除[Ca2+]i的这种升高，这表明钙内流途径参与其中。事实上，将钙通道阻滞剂尼群地平添加到PTH刺激的leq中可部分阻断PTH激活的钠转运。综上所述，这些数据表明PTH刺激A6细胞中的电生性钠转运，并且这种作用可能通过细胞内钙和细胞cAMP的升高来介导。
