Efflux of Probenecid-14C from Surviving Rabbit Renal Cortex Slices

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Abstract
Free-hand slices were prepared and permitted to accumulate probenecid from a balanced salt solution containing, this material (label and carrier) in a total concentration of 10-3 [image]. After rinsing, the tissue was transferred at 1-min. intervals through a series of beakers each containing 3.0 ml of modified, probenecid-free, Krebs-Ringer phosphate solution. The probenecid content of each beaker was determined by analysis of the 14C with a gas flow counter. Runout curves were constructed from these data and the amount of probenecid remaining in the tissue at the end of the efflux period. The mean first order rate constant was found to be significantly higher than that for urate or PAH [para aminohippurate] efflux (0.086 min.-1 for probenecid versus 0.065 min.-1 for urate and PAH). The runout process for probenecid was temperature sensitive with Q10 values ranging from 1.4 to 1.8 depending on the temperature range studied. Various substances which modify organic acid transport in kidney were studied by incorporating them in the runout solution. Succinate (10-2 [image]), acetate (10-2 [image]), iodoacetamide (5 x 10-4 M),p-aminohippurate (10-6 [image] to 10-3 [image]), and bromcresol green (10-5 [image] to 10-3 [image]) failed to alter the rate of efflux. p-Chloromercuribenzoate, 2,4-dinitrophenol and octanoate enhanced the efflux. The influence of pH on the runout process was also evaluated. The runout rate was directly proportional to the pH of the efflux solution over the range of pH 4.0 to pH 9.0.