Evidence for an inhibitor of renal urate and PAH secretion in rabbit blood.

Abstract

Results of previous studies of urate secretion in isolated perfused S2 segments of the rabbit proximal tubule suggested that a bath of rabbit serum may inhibit urate transport in comparison to a synthetic medium. In the current study we tested for a urate transport inhibitor by determining the steady-state tissue-to-medium ratio (T/M) of [14C]urate in nonperfused S2 segments during incubation in synthetic medium (BSA-Burg) and commercial rabbit serum (RS-PF). With 80-120 microM urate in the bath the T/M ratio was 7.66 +/- 0.53 (n = 29) in BSA-Burg and 5.29 +/- 0.40 (n = 29) in RS-PF. RS-PF decreased the influx of urate into the cells but had no effect on urate efflux. Freshly drawn rabbit serum and plasma also inhibited urate accumulation, and the inhibition was reversible. p-Aminohippurate accumulation was inhibited by RS-PF, but tetraethylammonium bromide uptake was not. RS-PF inhibited transepithelial secretion of urate and PAH, but net fluid absorption was not decreased. The inhibitory material in rabbit serum could not be removed by extensive dialysis (14,000-dalton exclusion), by ultrafiltration (50,000-dalton exclusion), or by charcoal or ethanol extraction. Inhibitory activity was detected in both albumin and globulin fractions of rabbit serum. The relation between bath and intracellular urate concentrations of nonperfused tubules in rabbit serum was sigmoidal, whereas the relation in the BSA-Burg medium was more nearly hyperbolic. We conclude that organic anion transport in rabbit S2 segments is inhibited or suppressed by normal serum and suggest that urate secretion and excretion may be subject to allosteric modification by serum proteins.