Multiple pathways of organic anion secretion in renal proximal tubule revealed by confocal microscopy

The American Journal of Physiology
R MasereeuwD S Miller

Abstract

Previous studies with p-aminohippurate (PAH) and fluorescein (FL) have shown that cellular uptake and tubular secretion of organic anions is driven by indirect coupling to sodium. Here we used killifish proximal tubules and laser-scanning confocal microscopy to study the transport of a larger organic anion, fluorescein-methotrexate (FL-MTX, mol mass 923 Da). When tubules were incubated in medium containing 2 microM FL-MTX, dye accumulated in both cells and tubular lumens. At steady state, luminal fluorescence was 4-5 times higher than cellular fluorescence. Ouabain (0.1 mM) did not affect cellular or luminal fluorescence, and replacement of medium sodium by N-methylglucamine had only a modest effect; preincubation with glutarate had no effect. KCN did not affect cellular uptake but abolished secretion into the lumen. Uptake and secretion of FL-MTX were inhibited by micromolar concentrations of other organic anions (MTX, folate, probenecid, bromocresol green, bromosulfophthalein), but 1 mM PAH had a relatively small effect. FL-MTX secretion into the lumen was inhibited by leukotriene C4, cyclosporine A, and verapamil, none of which affected FL transport. Thus a substantial component of FL-MTX secretion is Na independent and ouab...Continue Reading

Citations

Sep 21, 2000·American Journal of Physiology. Renal Physiology·R A Van AubelF G Russel
Dec 18, 2001·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·David S MillerGert Fricker
Feb 8, 2002·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·David S MillerKarl J Karnaky
Feb 8, 2002·American Journal of Physiology. Renal Physiology·Sylvia NotenboomRosalinde Masereeuw
Feb 19, 2004·American Journal of Physiology. Renal Physiology·Sylvia NotenboomRosalinde Masereeuw
Sep 15, 2007·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Valeska ReichelGert Fricker
Apr 26, 2011·The Journal of Pharmacology and Experimental Therapeutics·Brigitte PrevooRosalinde Masereeuw
Apr 23, 2004·American Journal of Physiology. Cell Physiology·Ruben M SandovalBruce A Molitoris
Sep 29, 2006·Antimicrobial Agents and Chemotherapy·Adrian S RayGerry R Rhodes
Oct 29, 2000·American Journal of Physiology. Renal Physiology·A ShuprishaW H Dantzler
Apr 6, 2002·American Journal of Physiology. Renal Physiology·Christopher M BreenDavid S Miller
Aug 17, 2006·American Journal of Physiology. Renal Physiology·Kim E WeverGert Flik
Aug 5, 2000·American Journal of Physiology. Renal Physiology·R A Van AubelF G Russel
Feb 5, 2002·Annual Review of Physiology·Frans G M RusselRemon A M H van Aubel
Jan 18, 2022·American Journal of Physiology. Renal Physiology·Jan Stephan BoltenJörg Huwyler

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