Regulation of Two Renal Chloride Transporters, AE1 and Pendrin, by Electrolytes and Aldosterone

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 NaHCO(3) and DOCA enhanced pendrin mRNA and protein levels, whereas DOCA or NaHCO(3) alone had no effect. NaCl or KHCO(3) increased pendrin mRNA, KCl decreased its mRNA abundance. On protein level, NH(4)Cl, 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, NaHCO(3)/DOCA or NaHCO(3) alone enhanced AE1 mRNA levels. AE1 protein abundance was increased by NH(4)Cl, NaHCO(3)/DOCA, and NaCl. Immunolocalization showed that during NH(4)Cl 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 NaHCO(3).