Is uric acid transported by the hippurate transport system?

Abstract

Experiments were designed to determine whether renal excretion of uric acid is achieved by the same mechanism as for renal tubular excretion of hippurates and related organic acids. Surviving slices of rabbit kidney cortex were unable to accumulate C14-urate by a concentrative mechanism. Further, entry of C14-urate into renal slices was unaffected by acetate, probenecid or anoxia in accord with earlier observations from this laboratory with non-radioactive urate. Experience with isolated perfused rat liver supports the use of this experimental method as a model of the hippurate transport system. Unlike hippurate and a large number of related organic anions, neither urate nor C14-activity derived from urate was concentrated in the bile from this preparation. Probenecid did not inhibit excretion of the small amounts of C14-activity which did appear in the bile. Urate did not compete with indigo carmine, a nonmetabolizable substrate of the hippurate transport system, for excretion into the bile. From these findings, it is concluded that urate and organic acids such as hippurate do not behave similarly in kidney or in liver. The possibility that urate might be excreted by an independent active transport mechanism is not excluded. The demonstration that renal tissues can synthesize urate from hypoxanthine raises the possibility that urate synthesis might also occur in the intact animal and might contribute to the renal clearance of uric acid.