Dual pathways for organic anion secretion in renal proximal tubule
✍ Scribed by Miller, David S.; Pritchard, John B.
- Publisher
- John Wiley and Sons
- Year
- 1997
- Tongue
- English
- Weight
- 425 KB
- Volume
- 279
- Category
- Article
- ISSN
- 0022-104X
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✦ Synopsis
Transport on the "classical" organic anion system in renal proximal tubule is specific, active, Na-dependent, and ouabain sensitive. Here we review recent studies using intact teleost proximal tubules and laser scanning confocal microscopy which show that the secretion of large organic anions, such as, fluorescein-methotrexate (FL-MTX, Mw 923 Da) is handled by a separate and distinct organic anion transport system. In contrast to the classical system, FL-MTX uptake into cells and secretion into the tubular lumen was ouabain insensitive and largely Na-independent. KCN did not affect cellular uptake but abolished secretion into the lumen. PAH and probenecid, potent inhibitors of transport on the classical system, were weak inhibitors of FL-MTX transport. Uptake and secretion of FL-MTX were inhibited by micromolar concentrations of other organic anions (MTX, folate, bromocresol green, bromosulfonphthalein). FL-MTX secretion into the lumen was inhibited by leukotriene C4 and cyclosporine A, neither of which affected transport of the model substrate for the classical system, fluorescein. Thus, FL-MTX secretion is specific, but largely Na-independent and ouabain-insensitive. Both the basolateral and luminal steps in FL-MTX transport differ from those associated with fluorescein and P-aminohippurate secretion.