In vitro Accumulation of ¹⁴C-Xanthine by Rabbit Renal Cortex and its Relationship to Overall Oxypurine Transport

Abstract

Previous detailed studies of the transport of hypoxanthine and uric acid indicate that these two oxypurines are handled by rather different processes. This report gives information on another important oxypurine, xanthine. Rabbit renal cortex slices were found to accumulate ¹⁴C-xanthine to concentrations significantly above those in the bathing solution (slice: medium or S/M ratios of about 2.0). This uptake is energy dependent as indicated by the effects of metabolic inhibitors. Carrier mediation was also probably involved and a relatively sharp pH optimum was noted. A requirement for potassium was also observed, but it was not nearly as marked as that seen for uric acid. Various agents (proben-ecid, octanoate, decanoate, etc.) known to inhibit organic acid transport were tested and found to reduce xanthine uptake significantly. The non-metabolizable amino acid, α-aminoisobutyric acid, did not block accumulation, however. Several organic bases were also without effect. A most significant finding was that several purine substances (including adenine and guanine) did not block accumulation. In general these data indicate that xanthine is transported mainly by the organic acid transport system (i.e. p-aminohippurate system) and not by the processes that handle hypoxanthine.