RT Journal Article
SR Electronic
T1 Kinetic analysis of the renal handling of 2,2-bis(p-chlorophenyl) acetic acid by the rat.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 9
OP 18
VO 205
IS 1
A1 J B Pritchard
YR 1978
UL http://jpet.aspetjournals.org/content/205/1/9.abstract
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.