Efflux of probenecid-14-C from surviving rabbit renal cortex slices.

Abstract

The runout of ring-labeled probencid ¹⁴C from preloaded slices of rabbit kidney cortex has been investigated. 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 M. 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 efflux (0.086 min^-1 for probenecid <i>versus </i>0.065 min^-1 for urate and PAH). The runout process for probenecid was temperature sensitive with Qio values ranging from 1.4 to 1.8 depending on the temperature range studied. Various substances which are known to modify organic acid transport in kidney were studied by incorporating them in the runout solution. Succinate (10^-2 M), acetate (10^–2 M), iodoacetamide 5 × 10^-4 M), p-aminohippurate (10^–6 M to 10^–3 M), and bromcresol green (10^-5 M to 10^-3 M) failed to alter the rate of runout. p-Chloromercuribenzoate, 2,4-dinitroρhenol and octanoate enhanced the efflux. The influence of pH on the runout process was also evaluated. The runout rate was found to be directly proportional to the pH of the efflux solution over the range of pH 4.0 to pH 9.0.