EFFECTS OF FORMATE AND OXALATE ON CHLORIDE ABSORPTION IN RAT DISTAL TUBULE

We previously demonstrated that formate and oxalate stimulate Cl- transport in the rat proximal tubule in accord with a model involving NaCl uptake across the luminal membrane via Cl-/organic anion exchange in parallel with Na+/H+ exchange and organic acid recycling. The purpose of the present study was to test whether similar mechanisms contribute to Cl- transport in the rat distal tubule. In distal tubules microperfused in situ with an isotonic solution, addition of 0.5 mM formate to the luminal perfusate increased Cl- (J(Cl)) and fluid (J(v)) absorption by 77 and 93%, respectively. Addition of 5 muM oxalate increased J(Cl) and J(v) by 52 and 108%, respectively. In distal tubules perfused with a hypotonic solution, formate stimulated J(Cl) and J(v) by 85 and 98%, respectively, and oxalate stimulated J(Cl) and J(v) by 80 and 115%, respectively. Addition of 0.5 mM acetate caused no significant change in J(Cl) and J(v). The stimulation of J(Cl) and J(v) by formate was largely abolished by addition of 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (100 muM) or ethylisopropylamiloride (10 muM) to the luminal perfusate. Chlorothiazide (0.5 mM) inhibited baseline J(Cl) and J(v) but caused no inhibition of the increments in J(v) and J(Cl) induced by formate. Formate stimulation of J(Cl) and J(v) was confined to early segments of the distal tubule. We conclude that formate and oxalate markedly enhance J(Cl) and J(v) in the early distal tubule by a thiazide-insensitive mechanism involving NaCl entry across the apical membrane by Cl-/organic anion exchange in parallel with Na+/H+ exchange.