Dual pathways for organic anion secretion in renal proximal tubule

J Exp Zool. 1997 Dec 1;279(5):462-70. doi: 10.1002/(sici)1097-010x(19971201)279:5<462::aid-jez8>3.0.co;2-m.


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.

Publication types

  • Review

MeSH terms

  • Animals
  • Biological Transport
  • Fishes / physiology
  • Fluoresceins / metabolism
  • Ion Pumps / physiology*
  • Kidney Tubules, Proximal / physiology*
  • Methotrexate / metabolism
  • Organic Chemicals / metabolism
  • Ouabain / administration & dosage


  • Fluoresceins
  • Ion Pumps
  • Organic Chemicals
  • Ouabain
  • Methotrexate