Abstract

Although there is no significant cephaloridine secretion into the urine, there is active cortical cephaloridine uptake by the p-aminohippurate (PAH) secretory carrier in the rabbit kidney. Studies were designed to examine in rabbit the mechanism by which this unusual transport process occurs. Quantities of PAH sufficient to inhibit virtually all cortical cephaloridine uptake did not result in cephaloridine clearance rates lower than those of inulin. Thus, evidence is lacking that cephaloridine is secreted and reabsorbed by different transport carriers. In vivo cortical cephaloridine and PAH concentrations were then measured using manipulations designed to allow comparison of their movement from the proximal tubular cell into the tubular fluid. Ureteral ligation interrupts the movement of PAH from proximal tubular fluid into the urine and therefore retards PAH movement from cell water to luminal fluid. Six minutes of ureteral ligation resulted in a doubling of in vivo renal cortical PAH concentration but had no effect on cortical cephaloridine concentration. Abrupt inhibition of transport by an intravenous bolus of probenecid results in a rapid loss of PAH from proximal tubular cells, primarily through the highly permeable luminal cell membrane into the tubular fluid and then into the urine. Intravenous probenecid resulted in a significantly more rapid decrease of the cortical concentration of PAH than that of cephaloridine. It is concluded that cephaloridine is transported into the proximal tubular cell at the peritubular cell membrane, but does not move readily across the luminal cell membrane into the tubular fluid. The unusually high intracellular cephaloridine concentration which results from this process may be partly responsible for the drug's toxicity to proximal tubular cells.