Department of Nephrology, Second University of Naples, Naples, Italy.
Kidney Int. 2013 Aug;84(2):277-84. doi: 10.1038/ki.2013.137. Epub 2013 Apr 24.
The proximal tubule uses a complex process of apical acid secretion and basolateral bicarbonate absorption to regulate both luminal acidification and fluid absorption. One of the primary regulators of apical acid secretion is the luminal sodium-hydrogen exchanger expressed along the apical membrane of the proximal tubule. Similarly, the calcium-sensing receptor (CaSR) is also located along the luminal membrane of the proximal tubule. Here we investigated the role of CaSR in proton secretion and fluid reabsorption in proximal tubules by modulating luminal calcium concentration, using both in vivo micropuncture in rats and in vitro perfused mouse proximal tubules. Using CaSR knockout mice and a calcimimetic agent, we found that increased proton secretion and fluid reabsorption were CaSR dependent. Activating CaSR by either raising the luminal calcium ion concentration or by the calcimimetic caused a concomitant increase in sodium-dependent proton extrusion and fluid reabsorption, whereas in proximal tubules isolated from CaSR knockout mice varying calcium ion concentration had no effect. Application of a calcimimetic in lower concentrations of calcium ion stimulated these processes in vitro and in vivo. Thus, in both rats and mice, increased luminal calcium concentration leads to enhanced fluid reabsorption in the proximal tubule, a process related to activation of CaSR.
近端小管通过顶端的酸分泌和基底外侧的碳酸氢盐吸收的复杂过程来调节管腔酸化和液体吸收。顶端酸分泌的主要调节剂之一是沿近端小管顶端膜表达的腔钠-氢交换器。同样，钙敏感受体 (CaSR) 也位于近端小管的腔膜上。在这里，我们通过调节腔内钙离子浓度，使用体内大鼠微穿刺和体外灌注的小鼠近端小管，研究了 CaSR 在近端小管质子分泌和液体重吸收中的作用。使用 CaSR 敲除小鼠和钙敏感受体激动剂，我们发现增加质子分泌和液体重吸收是 CaSR 依赖性的。通过提高腔钙离子浓度或使用钙敏感受体激动剂激活 CaSR 会导致钠依赖性质子外排和液体重吸收同时增加，而在从 CaSR 敲除小鼠分离的近端小管中，腔钙离子浓度的变化没有影响。在较低钙离子浓度下应用钙敏感受体激动剂可在体外和体内刺激这些过程。因此，在大鼠和小鼠中，增加腔内钙离子浓度可导致近端小管中液体重吸收增加，这一过程与 CaSR 的激活有关。
