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Research ArticleArticle

Chlorotrifluoroethylcysteine Interaction with Rabbit Proximal Tubule Cell Basolateral Membrane Organic Anion Transport and Apical Membrane Amino Acid Transport

Carlotta E. Groves and Mark N. Morales
Journal of Pharmacology and Experimental Therapeutics November 1999, 291 (2) 555-561;
Carlotta E. Groves
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Abstract

The interaction of the cysteine conjugateS-(1-chloro-1,2,2,-trifluoroethyl)-l-cysteine (CTFC) with organic anion and amino acid transport in the basolateral and apical membranes was examined with rabbit renal proximal tubule suspensions and primary cultures of rabbit renal proximal tubule cells. The apparent Ki for CTFC inhibition of the 1-min uptake of [3H]p-aminohippurate in tubule suspensions was 105 ± 3 μM and suggests that CTFC interacts with basolateral organic anion transport. Also, the addition of 1 mM CTFC decreased the secretion and intracellular accumulation of fluorescein by ∼70 to 75%. The addition of 1 mM CTFC to the apical compartment decreased the reabsorption and intracellular accumulation of the amino acid [3H]phenylalanine by ∼60 to 70%. Similar to CTFC, saturating concentrations of the organic anion [3H]p-aminohippurate and the amino acid phenylalanine reduced by ∼75% fluorescein secretion and [3H]phenylalanine reabsorption, respectively, by ∼60 to 70%. Thus, the cysteine conjugate CTFC appears to be a potent inhibitor of basolateral organic anion and apical amino acid transepithelial transport. In contrast to its effects on apical phenylalanine uptake, CTFC had no effect on the basal uptake of [3H]phenylalanine by primary cultures. The presence of CTFC in the external bath did trans-stimulate the efflux of fluorescein and [3H]phenylalanine across the basal and apical membrane in tubule suspensions or primary cultures, respectively, grown on plastic. Collectively, these data demonstrate that CTFC interacts with, and is transported by, two anatomically and functionally distinct transporters, the basolateral organic anion and apical neutral amino acid pathways, in the rabbit renal proximal tubule cell.

Footnotes

  • Send reprint requests to: Dr. Carlotta E. Groves, University of Florida, College of Veterinary Medicine, Department of Physiological Sciences, Center for Environmental and Human Toxicology, P.O. Box 110885, Gainesville, FL 32611-0885. E-mail:grovesce{at}mail.vetmed.ufl.edu

  • ↵1 This work was supported by National Institutes of Health Award ES-08860 and an American Heart Association Faculty Development Award. Portions of this work were presented at the 37th annual Society of Toxicology meeting, Seattle, WA, March 1998.

  • Abbreviations:
    CTFC
    S-(1-chloro-1,2,2-trifluoroethyl)-l-cysteine
    BBMV
    brush-border membrane vesicles
    DCVC
    S-(1,2-dichlorovinyl)-l-cysteine
    FL-I
    fluorescein isothiocyanate-inulin
    PAH
    p-aminohippurate
    PCBC
    S-(1,2,3,4,4-pentachlorobutadienyl)-l-cysteine
    PEC
    S-(1,2-phenylhydroxyethyl)-l-cysteine
    RPT
    renal proximal tubule
    TFEC
    S-(1,1,2,2-tetrafluoroethyl)-l-cysteine
    • Received April 23, 1999.
    • Accepted July 22, 1999.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 291 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 291, Issue 2
1 Nov 1999
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Research ArticleArticle

Chlorotrifluoroethylcysteine Interaction with Rabbit Proximal Tubule Cell Basolateral Membrane Organic Anion Transport and Apical Membrane Amino Acid Transport

Carlotta E. Groves and Mark N. Morales
Journal of Pharmacology and Experimental Therapeutics November 1, 1999, 291 (2) 555-561;

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Research ArticleArticle

Chlorotrifluoroethylcysteine Interaction with Rabbit Proximal Tubule Cell Basolateral Membrane Organic Anion Transport and Apical Membrane Amino Acid Transport

Carlotta E. Groves and Mark N. Morales
Journal of Pharmacology and Experimental Therapeutics November 1, 1999, 291 (2) 555-561;
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