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1 Institut National de la Santé et de la Recherche Médicale Unité 356, Institut Fédératif de Recherche 58, Université Pierre et Marie Curie, 75270 Paris Cedex 06; and 2 Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, 75908 Paris Cedex 15, France
In the proximal tubule, the apical Na+/H+ exchanger identified as NHE3 mediates most NaCl and NaHCO3 absorption. The purpose of this study was to analyze the long-term regulation of NHE3 during alkalosis induced by dietary NaHCO3 loading and changes in NaCl intake. Sprague-Dawley rats exposed to a low-NaCl, high-NaCl, or NaHCO3 diet for 6 days were studied. Renal cortical apical membrane vesicles (AMV) were prepared from treated and normal rats. Na+/H+ exchange was assayed as the initial rate of 22Na+ uptake in the presence of an outward H+ gradient. 22Na+ uptake measured in the presence of high-dose 5-(N-ethyl-N-isopropyl) amiloride was not different among models. Changes in NaCl intake did not affect NHE3 activity, whereas NaHCO3 loading inhibited 22Na+ uptake by 30%. AMV NHE3 protein abundance assessed by Western blot analysis was unaffected during changes in NaCl intake. During NaHCO3 loading, NHE3 protein abundance was decreased by 65%. We conclude that proximal NHE3 adapts to chronic metabolic acid-base disorders but not to changes in dietary NaCl intake.
sodium-hydrogen exchanger type 3; epithelial sodium-hydrogen exchanger; proximal tubule; acid-base status; sodium balance; sodium chloride
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