Hafner Patricia, Grimaldi Rosa, Capuano Paola, Capasso Giovambattista, Wagner Carsten A
Institute of Physiology and Zurich Center for Integrative Human Physiology, University of Zurich, Winterthurerstrasse 190, Zurich CH-8057, Switzerland.
Am J Physiol Cell Physiol. 2008 Dec;295(6):C1658-67. doi: 10.1152/ajpcell.00419.2008. Epub 2008 Oct 29.
The Cl(-)/anion exchanger pendrin (SLC26A4) is expressed on the apical side of renal non-type A intercalated cells. The abundance of pendrin is reduced during metabolic acidosis induced by oral NH(4)Cl loading. More recently, it has been shown that pendrin expression is increased during conditions associated with decreased urinary Cl(-) excretion and decreased upon Cl(-) loading. Hence, it is unclear if pendrin regulation during NH(4)Cl-induced acidosis is primarily due the Cl(-) load or acidosis. Therefore, we treated mice to increase urinary acidification, induce metabolic acidosis, or provide an oral Cl(-) load and examined the systemic acid-base status, urinary acidification, urinary Cl(-) excretion, and pendrin abundance in the kidney. NaCl or NH(4)Cl increased urinary Cl(-) excretion, whereas (NH(4))(2)SO(4), Na(2)SO(4), and acetazolamide treatments decreased urinary Cl(-) excretion. NH(4)Cl, (NH(4))(2)SO(4), and acetazolamide caused metabolic acidosis and stimulated urinary net acid excretion. Pendrin expression was reduced under NaCl, NH(4)Cl, and (NH(4))(2)SO(4) loading and increased with the other treatments. (NH(4))(2)SO(4) and acetazolamide treatments reduced the relative number of pendrin-expressing cells in the collecting duct. In a second series, animals were kept for 1 and 2 wk on a low-protein (20%) diet or a high-protein (50%) diet. The high-protein diet slightly increased urinary Cl(-) excretion and strongly stimulated net acid excretion but did not alter pendrin expression. Thus, pendrin expression is primarily correlated with urinary Cl(-) excretion but not blood Cl(-). However, metabolic acidosis caused by acetazolamide or (NH(4))(2)SO(4) loading prevented the increase or even reduced pendrin expression despite low urinary Cl(-) excretion, suggesting an independent regulation by acid-base status.
氯（Cl⁻）/阴离子交换体pendrin（SLC26A4）表达于肾非A型闰细胞的顶端。口服氯化铵负荷诱导代谢性酸中毒时，pendrin的丰度降低。最近研究表明，在尿Cl⁻排泄减少的情况下，pendrin表达增加，而给予Cl⁻负荷后pendrin表达降低。因此，尚不清楚氯化铵诱导酸中毒期间pendrin的调节主要是由于Cl⁻负荷还是酸中毒。为此，我们对小鼠进行处理以增加尿液酸化、诱导代谢性酸中毒或给予口服Cl⁻负荷，并检测全身酸碱状态、尿液酸化、尿Cl⁻排泄以及肾脏中pendrin的丰度。氯化钠或氯化铵增加尿Cl⁻排泄，而硫酸铵、硫酸钠和乙酰唑胺处理则减少尿Cl⁻排泄。氯化铵、硫酸铵和乙酰唑胺导致代谢性酸中毒并刺激尿净酸排泄。在氯化钠、氯化铵和硫酸铵负荷下，pendrin表达降低，而其他处理则使其表达增加。硫酸铵和乙酰唑胺处理减少了集合管中表达pendrin细胞的相对数量。在第二项实验中，动物分别给予低蛋白（20%）饮食或高蛋白（50%）饮食1周和2周。高蛋白饮食轻度增加尿Cl⁻排泄并强烈刺激净酸排泄，但未改变pendrin表达。因此，pendrin表达主要与尿Cl⁻排泄相关，而与血Cl⁻无关。然而尽管尿Cl⁻排泄减少，但乙酰唑胺或硫酸铵负荷引起的代谢性酸中毒却阻止了pendrin表达的增加甚至使其降低，提示酸碱状态存在独立调节作用。
