Uric acid transport in brush border membrane vesicles isolated from rabbit kidney

Abstract

The transport of uric acid was studied in brush border membrane vesicles isolated from rabbit kidney. The uptake of uric acid by the vesicles was osmotically sensitive and occurred in the absence of significant uric acid degradation. Under the conditions used to evaluate transport, urate binding to the membranes represented only 10--15% of the total uptake. The initial rate of uptake was linear over the concentration range 0.04--8 mM urate. Uptake of urage was Na+ gradient independent. It was dependent on external pH and temperature with Q10 near 3. The urate uptake was inhibited reversibly by p-chloromercuribenzoate. Probenecid, ouabain, cyclic adenosine 3',5'--monophosphate, and its dibutyryl derivative had no appreciable effects. Pyrazinoic acid and pyrazinamide stimulated urate uptake. Experiments performed with osmotically shocked vesicles demonstrated that this stimulatory effect resulted from increased binding of urate to the membranes. These results indicate that in several ways urate transport in vesicles resembles that observed with more physiologically intact preparations.

Renal Pathogenesis of Familial Hyperuricemia: Studies in Two Kindreds

“…It appears that reabsorption of uric acid is an active process (25); the concentration of uric acid in proximal tubular fluid decreases below plasma levels to a degree which could not be maintained by transepithelial potential difference. This conclusion is supported by data from studies of uric acid transport in brush-border vesicles (5,7). Other factors that affect the proximal tubule reabsorption of uric acid include the rate of urine flow, the concentration of glucose in the urine, and the pH gradient (5, 6, 15.…”