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This Article Full Text Full Text (PDF) All Versions of this Article: 297/2/F440    most recent 90318.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Busque, S. M. Articles by Wagner, C. A. PubMed PubMed Citation Articles by Busque, S. M. Articles by Wagner, C. A.

Potassium restriction, high protein intake, and metabolic acidosis increase expression of the glutamine transporter SNAT3 (Slc38a3) in mouse kidney

Institute of Physiology, Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland

Submitted 18 May 2008 ; accepted in final form 17 May 2009

Kidneys produce ammonium to buffer and excrete acids through metabolism of glutamine. Expression of the glutamine transporter Slc38a3 (SNAT3) increases in kidney during metabolic acidosis (MA), suggesting a role during ammoniagenesis. Potassium depletion and high dietary protein intake are known to elevate renal ammonium excretion. In this study, we examined SNAT3, phosphate-dependent glutaminase (PDG), and phosphoenolpyruvate carboxykinase (PEPCK) regulation during a control (0.36%) or low-K⁺ (0.02%) diet for 7 or 14 days or a control (20%) or high-protein (50%) diet for 7 days. MA was induced in control and low-K⁺ groups by addition of NH₄Cl. Urinary ammonium excretion increased during MA, after 14-day K⁺ restriction alone, and during high protein intake. SNAT3, PDG, and PEPCK mRNA abundance were elevated during MA and after 14-day K⁺ restriction but not during high protein intake. SNAT3 protein abundance was enhanced during MA (both control and low K⁺), after 14-day low-K⁺ treatment alone, and during high protein intake. Seven-day dietary K⁺ depletion alone had no effect. Immunohistochemistry showed SNAT3 staining in earlier parts of the proximal tubule during 14-day K⁺ restriction with and without NH₄Cl treatment and during high protein intake. In summary, SNAT3, PDG, and PEPCK mRNA expression were congruent with urinary ammonium excretion during MA. Chronic dietary K⁺ restriction, high protein intake, and MA enhance ammoniagenesis, an effect that may involve enhanced SNAT3 mRNA and protein expression. Our data suggest that SNAT3 plays an important role as the glutamine uptake mechanism in ammoniagenesis under these conditions.

glutamine transporters; renal ammoniagenesis; phosphate-dependent glutaminase; phosphoenolpyruvate carboxykinase