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Research ArticleArticle

Active Lucifer Yellow Secretion in Renal Proximal Tubule: Evidence for Organic Anion Transport System Crossover

Rosalinde Masereeuw, Miek M. Moons, Barbara H. Toomey, Frans G. M. Russel and David S. Miller
Journal of Pharmacology and Experimental Therapeutics May 1999, 289 (2) 1104-1111;
Rosalinde Masereeuw
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Miek M. Moons
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Barbara H. Toomey
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Frans G. M. Russel
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David S. Miller
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Abstract

Recent studies show that organic anion secretion in renal proximal tubule is mediated by distinct sodium-dependent and sodium-independent transport systems. Here we investigated the possibility that organic anions entering the cells on one system can exit into the lumen on a transporter associated with the other system. In isolated rat kidneys perfused with 10 μM lucifer yellow (LY, a fluorescent organic anion) plus 100 μg/ml inulin, the LY-to-inulin clearance ratio averaged 1.6 ± 0.2, indicating net tubular secretion. Probenecid significantly reduced both LY clearance and LY accumulation in kidney tissue. In intact killifish proximal tubules, confocal microscopy was used to measure steady-state LY uptake into cells and secretion into the tubular lumen. Probenecid, p-aminohippurate, and ouabain nearly abolished both uptake and secretion. To this point, the data indicated that LY was handled by the sodium-dependent and ouabain-sensitive organic anion transport system. However, leukotriene C4, an inhibitor of the luminal step for the sodium-independent and ouabain-insensitive organic anion system, reduced luminal secretion of LY by 50%. Leukotriene C4 did not affect cellular accumulation of LY or the transport of fluorescein on the sodium-dependent system. A similar inhibition pattern was found for another fluorescent organic anion, a mercapturic acid derivative of monochlorobimane. Thus, both organic anions entered the cells on the basolateral transporter for the classical, sodium-dependent system, but about half of the transport into the lumen was handled by the luminal carrier for the sodium-independent system, which is most likely the multidrug resistance-associated protein. This is the first demonstration that xenobiotics can enter renal proximal tubule cells on the carrier associated with one organic anion transport system and exit into the tubular lumen on multiple carriers, one of which is associated with a second system.

Footnotes

  • Send reprint requests to: Rosalinde Masereeuw, Ph.D., Department of Pharmacology 233, Faculty of Medical Sciences, University of Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, the Netherlands. E-mail:R.Masereeuw{at}farm.kun.nl

  • ↵1 This study was supported by a grant from the Dutch Kidney Foundation (Grant C.90.1047).

  • Abbreviations:
    LY
    lucifer yellow
    LTC4
    leukotriene C4
    MCB
    monochlorobimane
    CDNB
    1-chloro-2,4-dinitrobenzene
    FL
    fluorescein
    FL-MTX
    FL-methotrexate
    PAH
    p-aminohippurate
    Mrp2
    multidrug resistance-associated protein 2
    GFR
    glomerular filtration rate
    • Received October 2, 1998.
    • Accepted December 30, 1998.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 289 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 289, Issue 2
1 May 1999
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Research ArticleArticle

Active Lucifer Yellow Secretion in Renal Proximal Tubule: Evidence for Organic Anion Transport System Crossover

Rosalinde Masereeuw, Miek M. Moons, Barbara H. Toomey, Frans G. M. Russel and David S. Miller
Journal of Pharmacology and Experimental Therapeutics May 1, 1999, 289 (2) 1104-1111;

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Research ArticleArticle

Active Lucifer Yellow Secretion in Renal Proximal Tubule: Evidence for Organic Anion Transport System Crossover

Rosalinde Masereeuw, Miek M. Moons, Barbara H. Toomey, Frans G. M. Russel and David S. Miller
Journal of Pharmacology and Experimental Therapeutics May 1, 1999, 289 (2) 1104-1111;
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