Organic cation transport in the rat kidney in vivo visualized by time-resolved two-photon microscopy

Kidney Int. 2007 Aug;72(4):422-9. doi: 10.1038/ Epub 2007 May 2.


Secretion of cationic drugs and endogenous metabolites is a major function of the kidney accomplished by tubular organic cation transport systems. A cationic styryl dye (ASP(+)) was developed as a fluorescent substrate for renal organic cation transporters. The dye was injected intravenously and continuously monitored in externalized rat kidneys by time-resolved two-photon laser scanning microscopy. To investigate changes in transport activity, cimetidine, a competitive inhibitor of organic cation transport was co-injected with ASP(+). Shortly after injection, fluorescence increased in peritubular capillaries. Simultaneously, fluorescence was transiently found at the basolateral membrane of the proximal and distal tubules at a higher intensity and shorter wavelength indicating membrane association of ASP(+). Subsequently, intracellular fluorescence increased steeply within 10 s. In the proximal tubules, intracellular fluorescence decreased by 50% within 5 min, while in the distal tubules the fluorescence decreased by only 5% within the same time frame. Intracellular uptake of ASP(+) into proximal tubules was significantly reduced by cimetidine. Our studies show that organic cation transport of the kidney can be visualized in vivo by two-photon laser scanning microscopy.

Publication types

  • Evaluation Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Biological Transport
  • Cations / metabolism
  • Cimetidine / pharmacology
  • Fluorescent Dyes / administration & dosage
  • Fluorescent Dyes / metabolism*
  • Injections, Intravenous
  • Kidney / blood supply
  • Kidney / drug effects
  • Kidney / metabolism*
  • Kidney Tubules, Distal / metabolism
  • Kidney Tubules, Proximal / metabolism
  • Male
  • Microcirculation / metabolism
  • Microscopy, Confocal*
  • Microscopy, Fluorescence, Multiphoton*
  • Microscopy, Video*
  • Organic Cation Transport Proteins / antagonists & inhibitors
  • Organic Cation Transport Proteins / metabolism*
  • Pyridinium Compounds / administration & dosage
  • Pyridinium Compounds / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Reproducibility of Results
  • Time Factors


  • 4-(4-dimethylaminostyryl)-1-methylpyridinium
  • Cations
  • Fluorescent Dyes
  • Organic Cation Transport Proteins
  • Pyridinium Compounds
  • Cimetidine