Nagami Glenn T, Chang Jenny A, Plato Megan E, Santamaria Rafael
Nephrology Section, Mail code 111L, VA Greater Los Angeles Healthcare System, 11301 Wilshire Blvd., Los Angeles, CA 90073, USA.
Am J Physiol Renal Physiol. 2008 Dec;295(6):F1864-70. doi: 10.1152/ajprenal.90410.2008. Epub 2008 Oct 22.
The proximal tubule defends the body against acid challenges by enhancing its production and secretion of ammonia. Our previous studies demonstrated an enhanced ammoniagenic response of the proximal tubule to ANG II added to the lumen in vitro after an in vivo acid challenge. The present study examined the effect of NH(4)Cl acid loading in vivo on renal cortical type 1 ANG II (AT(1)) receptor expression, the effect of low pH on AT(1) receptor expression in a proximal tubule cells in culture, and their response to ANG II. A short-term (18 h) NH(4)Cl load in vivo resulted in increased renal cortical AT(1) receptor mRNA expression and increased brush-border membrane AT(1) receptor protein expression levels. Changing the cell culture pH from 7.4 to 7.0 for at least 2 h increased cell surface expression of AT(1) receptors and enhanced the stimulatory effect of ANG II on ammonia production rates. This increased ammoniagenic response to ANG II and the early enhancement of cell surface expression induced by exposure of the cultured proximal tubule cells to pH 7.0 were prevented by treatment with colchicine. These results suggest that, after acid challenges, the enhanced ammoniagenic response of the proximal tubule to ANG II is, in part, mediated by increased AT(1) receptor cell surface expression and that the enhancement of receptor expression plays an important role in the early response of the proximal tubule to acid challenges.
近端小管通过增强氨的生成和分泌来保护机体免受酸性物质的挑战。我们之前的研究表明，在体内酸性刺激后，体外向管腔中添加血管紧张素II（ANG II）时，近端小管的产氨反应增强。本研究检测了体内氯化铵酸负荷对肾皮质1型ANG II（AT(1)）受体表达的影响、低pH对培养的近端小管细胞中AT(1)受体表达的影响以及它们对ANG II的反应。体内短期（18小时）氯化铵负荷导致肾皮质AT(1)受体mRNA表达增加以及刷状缘膜AT(1)受体蛋白表达水平升高。将细胞培养的pH从7.4变为7.0至少2小时，可增加AT(1)受体的细胞表面表达，并增强ANG II对氨生成速率的刺激作用。用秋水仙碱处理可阻止培养的近端小管细胞暴露于pH 7.0时ANG II产氨反应增强以及细胞表面表达的早期增强。这些结果表明，在酸性刺激后，近端小管对ANG II产氨反应增强部分是由AT(1)受体细胞表面表达增加介导的，并且受体表达的增强在近端小管对酸性刺激的早期反应中起重要作用。
