Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-3215
Nowik, M; Picard, N; Stange, G; Capuano, P; Tenenhouse, H S; Biber, J; Murer, H; Wagner, C A (2008). Renal phosphaturia during metabolic acidosis revisited: molecular mechanisms for decreased renal phosphate reabsorption. Pflügers Archiv: European Journal of Physiology (Pflugers Archiv), 457(2):539-549.
During metabolic acidosis (MA), urinary phosphate excretion increases and contributes to acid removal. Two Na(+)-dependent phosphate transporters, NaPi-IIa (Slc34a1) and NaPi-IIc (Slc34a3), are located in the brush border membrane (BBM) of the proximal tubule and mediate renal phosphate reabsorption. Transcriptome analysis of kidneys from acid-loaded mice revealed a large decrease in NaPi-IIc messenger RNA (mRNA) and a smaller reduction in NaPi-IIa mRNA abundance. To investigate the contribution of transporter regulation to phosphaturia during MA, we examined renal phosphate transporters in normal and Slc34a1-gene ablated (NaPi-IIa KO) mice acid-loaded for 2 and 7 days. In normal mice, urinary phosphate excretion was transiently increased after 2 days of acid loading, whereas no change was found in Slc34a1-/- mice. BBM Na/Pi cotransport activity was progressively and significantly decreased in acid-loaded KO mice, whereas in WT animals, a small increase after 2 days of treatment was seen. Acidosis increased BBM NaPi-IIa abundance in WT mice and NaPi-IIc abundance in WT and KO animals. mRNA abundance of NaPi-IIa and NaPi-IIc decreased during MA. Immunohistochemistry did not indicate any change in the localization of NaPi-IIa and NaPi-IIc along the nephron. Interestingly, mRNA abundance of both Slc20 phosphate transporters, Pit1 and Pit2, was elevated after 7 days of MA in normal and KO mice. These data demonstrate that phosphaturia during acidosis is not caused by reduced protein expression of the major Na/Pi cotransporters NaPi-IIa and NaPi-IIc and suggest a direct inhibitory effect of low pH mainly on NaPi-IIa. Our data also suggest that Pit1 and Pit2 transporters may play a compensatory role.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > Center for Integrative Human Physiology|
04 Faculty of Medicine > Institute of Physiology
07 Faculty of Science > Institute of Physiology
|DDC:||570 Life sciences; biology|
610 Medicine & health
|Deposited On:||09 Sep 2008 14:07|
|Last Modified:||28 Nov 2013 00:31|
|Additional Information:||The original publication is available at www.springerlink.com|
|Citations:||Web of Science®. Times cited: 26|
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