KINETIC-ANALYSIS OF RENAL HANDLING OF 2,2-BIS (PARA-CHLOROPHENYL) ACETIC-ACID BY RAT

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  • 1 January 1978
    • journal article
    • research article
    • Vol. 205  (1) , 9-18
Abstract
The kinetics of uptake and efflux of organic acids in rat renal cortical slices were used to examine the affinity of 2,2-bis(p-chlorophenyl)acetic acid (DDA) for the organic acid transport system and to assess intracellular binding of this polar 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) metabolite. As judged by its ability to inhibit p-aminohippuric acid transport, DDA was a potent competitive inhibitor, almost as strong as probenecid, the classical inhibitor of this system. Efflux of DDA from slices demonstrated that the bulk (85%) of the DDA within the slice was reversibly bound to proteins or other macromolecules. Cortical slices incubated 60 min with 10 .mu.M DDA contained a total concentration of 160 .mu.M DDA within the tubular cells, but the actual free concentration in the cells was only 20-30 .mu.M. Although DDA was accumulated against a concentration gradient by the kidney, the gradient was much smaller than the measured tissue/medium ratio. Potential consequences of DDA exposure through its interaction with the organic acid system and roles of DDA binding sites in the toxicity and transport of DDA are discussed.