Uremic inhibition of purine uptake by rat hepatic slices

Measurements were made of the production of allantoin by liver slices prepared either from bilaterally nephrectomized rats or from normal, control rats in flasks containing either a) no added substrate, b) hypoxanthine, or c) xanthine. Uremic liver slices showed a 72.3% inhibition of augmented allantoin production with hypoxanthine as substrate and a 68.3% inhibition with xanthine as substrate. Next, uremic rat serum was added to liver slices prepared from normal rats along with either a) no added substrate, b) hypoxanthine, or c) xanthine. Normal rat serum replaced uremic rat serum in control experiments. In these paired experiments, uremic serum exerted an inhibitory effect on allantoin production of 78.0% when hypoxanthine was the substrate and of 83.6% when xanthine was the substrate. Studies on possible underlying mechanisms showed that the observed uremic inhibition of allantoin production by hepatic slices, in the presence of substrate (e.g., hypoxanthine), represents a decreased production of uric acid, secondary to the decreased hepatic uptake of substrate.