title: Regulation of two renal chloride transporters, AE1 and pendrin, by electrolytes and aldosterone.
abstract: The renal handling of salt and protons and bicarbonate are intricately linked through shared transport mechanisms for sodium, chloride, protons, and bicarbonate. In the collecting duct, the regulated fine-tuning of salt and acid-base homeostasis is achieved by a series of transport proteins located in different cell types, intercalated and principal cells. Intercalated cells are considered to be of less importance for salt handling but recent evidence has suggested that the anion exchanger pendrin may participate in salt reabsorption and blood pressure regulation. Here, we examined the regulated expression of two functionally related but differentially expressed anion exchangers, AE1 and pendrin, by dietary electrolyte intake and aldosterone. Cortical expression of pendrin was regulated on mRNA and protein level. The combination of NaHCO₃ and DOCA enhanced pendrin mRNA and protein levels, whereas DOCA or NaHCO₃ alone had no effect. NaCl or KHCO₃ increased pendrin mRNA, KCl decreased its mRNA abundance. On protein level, NH₄Cl, NaCl, and KCl reduced pendrin expression, the other treatments were without effect. In contrast, AE1 mRNA or protein expression in kidney cortex was regulated by none of these treatments. In kidney medulla, NaHCO₃/DOCA or NaHCO₃ alone enhanced AE1 mRNA levels. AE1 protein abundance was increased by NH₄Cl, NaHCO₃/DOCA, and NaCl. Immunolocalization showed that during NH₄Cl treatment the relative number of AE1 positive cells was increased and pendrin expressing cells reduced. Thus, pendrin and AE1 are differentially regulated with distinct mechanisms that separately affect mRNA and protein levels. Pendrin is regulated by acidosis and chloride intake, whereas AE1 is enhanced by acidosis, NaCl, and the combination of DOCA and NaHCO₃.
authors: Institute of Physiology and Zurich Center for Integrative Human Physiology-ZIHP, Zurich, Switzerland.
authors: Nilufar
authors: N
authors: Mohebbi
authors: Angelica
authors: A
authors: Perna
authors: Jenny
authors: J
authors: van der Wijst
authors: Helen M
authors: HM
authors: Becker
authors: Giovambattista
authors: G
authors: Capasso
authors: Carsten A
authors: CA
authors: Wagner
mesh_terms: D000450:Aldosterone / Q000378:metabolism*; D000643:Ammonium Chloride / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001457:Anion Exchange Protein 1, Erythrocyte / Q000378:metabolism*; D027321:Anion Transport Proteins / Q000378:metabolism*; D001639:Bicarbonates / Q000494:pharmacology; D015153:Blotting, Western; D002852:Chromatography, Ion Exchange; D003900:Desoxycorticosterone; D004573:Electrolytes / Q000378:metabolism* / Q000652:urine; D005786:Gene Expression Regulation / Q000187:drug effects*; D006863:Hydrogen-Ion Concentration; D007150:Immunohistochemistry; D007685:Kidney Tubules, Collecting / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017680:Potassium Compounds / Q000494:pharmacology; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017693:Sodium Bicarbonate / Q000494:pharmacology; D000076988:Sulfate Transporters
chemical_list: D001457:Anion Exchange Protein 1, Erythrocyte; D027321:Anion Transport Proteins; D001639:Bicarbonates; D004573:Electrolytes; D017680:Potassium Compounds; C494849:Slc26a4 protein, mouse; D000076988:Sulfate Transporters; D000643:Ammonium Chloride; D003900:Desoxycorticosterone; D000450:Aldosterone; D017693:Sodium Bicarbonate; C026329:potassium bicarbonate
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