Chlorotrifluoroethylcysteine interaction with rabbit proximal tubule cell basolateral membrane organic anion transport and apical membrane amino acid transport.
The interaction of the cysteine conjugate S-(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 K(i) for CTFC inhibition of the 1-min uptake of [(3)H]p-aminohippurate in tubule suspensions was 105+/-3 microM 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 approximately 70 to 75%. The addition of 1 mM CTFC to the apical compartment decreased the reabsorption and intracellular accumulation of the amino acid [(3)H]phenylalanine by approximately 60 to 70%. Similar to CTFC, saturating concentrations of the organic anion [(3)H]p-aminohippurate and the amino acid phenylalanine reduced by approximately 75% fluorescein secretion and [(3)H]phenylalanine reabsorption, respectively, by approximately 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 [(3)H]phenylalanine by primary cultures. The presence of CTFC in the external bath did trans-stimulate the efflux of fluorescein and [(3)H]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.
Groves
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Department of Physiological Sciences, University of Florida, College of Veterinary Medicine, Gainesville, Florida 32611-0885, USA. grovesce@mail.vetmed.ufl.edu
Morales
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MN
D000596:Amino Acids / Q000493:pharmacokinetics*; D000818:Animals; D000838:Anions / Q000493:pharmacokinetics*; D001693:Biological Transport, Active / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects*; D002478:Cells, Cultured; D003287:Contrast Media / Q000493:pharmacokinetics; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D005260:Female; D019793:Fluorescein / Q000493:pharmacokinetics; D007687:Kidney Tubules, Proximal / Q000187:drug effects*; D008297:Male; D010649:Phenylalanine / Q000494:pharmacology; D011817:Rabbits; D013997:Time Factors; D010130:p-Aminohippuric Acid / Q000493:pharmacokinetics
D000596:Amino Acids; D000838:Anions; D003287:Contrast Media; D010649:Phenylalanine; C047601:S-(2-chloro-1,1,2-trifluoroethyl)cysteine; D003545:Cysteine; D019793:Fluorescein; D010130:p-Aminohippuric Acid