EFFECTS OF FORMATE AND OXALATE ON VOLUME ABSORPTION IN RAT PROXIMAL TUBULE

We examined the effects of formate and oxalate on the rate of fluid absorption (J(v)) in the rat proximal convoluted tubule in situ. Proximal tubules were microperfused with a high-Cl-, low-HCO-3 Ringer solution (pH 6.7), and the peritubular capillaries were perfused with a standard Ringer solution (pH 7.4), simulating conditions in the late proximal tubule. J(v), a measure of transtubular NaCl absorption under these conditions, was calculated from the change in luminal [H-3]inulin. Addition of formate in the physiological range (500-mu-M) to the luminal perfusate increased J(v) by 45%; addition of 500-mu-M formate to both luminal and capillary perfusates increased J(v) by 57%. Similarly, addition of oxalate in the physiological range (5-mu-M) to the luminal perfusate increased J(v) by 37%; addition of 5-mu-M oxalate to both luminal and capillary perfusates increased J(v) by 57%. The stimulatory effects of formate and oxalate perfused in the lumen and capillaries were not additive. Addition of 4,4'-diisothiocyanostilbene-2,2'-disulfonate (DIDS, 0.1 mM) to the luminal perfusate had no effect on baseline J(v) measured in the absence of added formate and oxalate but completely abolished the increment in J(v) induced by formate and oxalate. Addition of the Cl--channel blocker diphenylamine-2-carboxylate (DPC, 0.2 mM) to the capillary perfusate had no effect on baseline J(v) but completely abolished the increment in J(v) induced by formate and oxalate. These results indicate that formate and oxalate play a critical role in promoting transcellular Cl- transport in the proximal tubule and are consistent with a model involving Cl- uptake across the luminal membrane via DIDS-sensitive anion exchange followed by Cl- exit across the basolateral membrane via DPC-sensitive Cl- channels.