Relation of Cysteine Conjugate Nephrotoxicity to Transport by the Basolateral Organic Anion Transport System in Isolated S2 Segments of Rabbit Proximal Renal Tubules
We examined basolateral transport of the radiolabeled zwitterionic nephrotoxic cysteine S -conjugate, S -(1,2-dichlorovinyl)- l -cysteine (DCVC), inhibition of such transport and the effects of inhibition of transport on the toxicity produced by DCVC in isolated S2 segments of rabbit proximal tubule...
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Published in | The Journal of pharmacology and experimental therapeutics Vol. 286; no. 1; p. 52 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Society for Pharmacology and Experimental Therapeutics
01.07.1998
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Subjects | |
Online Access | Get full text |
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Summary: | We examined basolateral transport of the radiolabeled zwitterionic nephrotoxic cysteine S -conjugate, S -(1,2-dichlorovinyl)- l -cysteine (DCVC), inhibition of such transport and the effects of inhibition of transport on the toxicity produced by DCVC
in isolated S2 segments of rabbit proximal tubules. High concentrations of unlabeled DCVC itself and an unlabeled nontoxic
cysteine S -conjugate, S -(2-benzothiazole)- l -cysteine cis -inhibited the basolateral uptake of radiolabeled DCVC by â¼80 to 85%. High concentrations of para-aminohippurate, the prototype
substrate for the basolateral organic anion transport system, and probenecid, a well-known inhibitor of basolateral organic
anion transport, cis -inhibited the basolateral uptake of radiolabeled DCVC by â¼70%, whereas a high concentration of l -phenylalanine had little effect. High concentrations of S -(2-benzothiazole)- l -cysteine and para-aminohippurate in the bathing medium with DCVC inhibited the loss of 86 Rb (used as a K + surrogate to measure toxicity) from S2 segments produced by DCVC alone to approximately the same extent as they inhibited
uptake of DCVC. Under the same circumstances, probenecid completely inhibited 86 Rb loss. These data indicate that in rabbit proximal renal S2 tubules basolateral entry of DCVC can occur to a major extent
via the organic anion transport pathway and that inhibition of such entry can reduce toxicity to approximately the same extent
that entry is reduced. They also suggest that probenecid provides additional protection from DCVC toxicity. |
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ISSN: | 0022-3565 1521-0103 |