PT  - JOURNAL ARTICLE
AU  - J B Pritchard
TI  - Kinetic analysis of the renal handling of 2,2-bis(p-chlorophenyl) acetic acid by the rat.
DP  - 1978 Apr 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 9--18
VI  - 205
IP  - 1
4099  - http://jpet.aspetjournals.org/content/205/1/9.short
4100  - http://jpet.aspetjournals.org/content/205/1/9.full
SO  - J Pharmacol Exp Ther1978 Apr 01; 205
AB  - 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 minutes with 10 micron DDA contained a total concentration of 160 micron DDA within the tubular cells, but the actual free concentration in the cells was only 20 to 30 micron. Thus, 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.