Possible role of anion exchanger AE2 as the intestinal monocarboxylic acid/anion antiporter

Purpose. The purpose of the present study was to investigate the transport of organic monocarboxylic acids mediated by the anion exchanger AE2, which has been already reported to be present at several tissue cell membranes, including intestinal brush border membrane in rabbit. Methods. Membrane transport of organic monocarboxylic acids by AE2 was investigated by transient AE2-gene expression in HEK 293 cells and subsequent uptake studies by the cells. Results. Functional transfection of AE2 was confirmed by the enhanced ³⁶Cl^- efflux from the cells. When preloaded with chloride anion, AE2-transfected cells demonstrated a significantly enhanced [¹⁴C]benzoic acid transport activity compared with mock-transfected cells. The AE2-mediated uptake was saturable with kinetic parameters of Km = 0.26 ± 0.08 mM and Vmax = 6.14 ± 0.52 nmol/mg/protein/ 3 min, and the uptake of [¹⁴C]benzoic acid was pH-dependent with a maximal uptake at pH 6.5. AE2-mediated [¹⁴C]benzoic acid uptake was inhibited by Cl^-, HCO₃^-, and DIDS. AE2-transfected cells demonstrated significantly enhanced transport activity for nicotinic acid, propionic acid, butyric acid, and valproic acid as well as benzoic acid compared with mock-transfected cells. Conclusions. AE2 is functionally involved in the anion antiport for organic monocarboxylic acids as well as inorganic anions and is supposed to play a partial role in the intestinal transport of organic acids.