Comparative accumulation of uric acid and hypoxanthine by slices of avian renal cortex

Abstract

The purpose of the study was to compare the concentrative uptake processes of the 14C-labeled purines uric acid (UA) and hypoxanthine (HX) by slices of chicken renal cortex. It was found that both purines were accumulated by the slices and that, while UA was unaltered metabolically, HX was partially oxidized to UA during the incubation. Inhibition of the oxidation of HX to UA by use of the enzyme inhibitor allopurinol did not alter accumulation indicating that metabolism of HX did not drive accumulation. UA accumulation was eliminated by the presence of low concentrations of the organic anion transport inhibitors probenecid and 4-acetamido-4'-isothiocyano-stilbene-2,2'-disulfonic acid. However, HX accumulation was unaffected by probenecid and significantly decreased by 4-acetamido-4'-isothiocyano-stilbene-2,2'-disulfonic acid only at concentrations considerably in excess of those needed to eliminate UA accumulation. The lack of effect of probenecid is in contrast to its reported inhibitory action on HX excretion by the chicken in vivo, a difference which may reflect lack of luminal transport by in vitro slices. Neither was HX accumulation sensitive to the presence of high concentrations of the organic cations quinine and tetraethylammonium. Despite the insensitivity of the HX accumulation process to organic anions or cations, the process was blocked by cyanide and an N2 atmosphere indicating energy dependence. The results suggest that both UA and HX are accumulated by separable transport processes indicating that the renal tubules possess more than one system capable of contributing to purine excretion.