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

M. Hörbelt, C. Wotzlaw, T. A. Sutton, B. A. Molitoris, T. Philipp, A. Kribben, J. Fandrey, F. Pietruck

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)422-429
Number of pages8
JournalKidney international
Volume72
Issue number4
DOIs
StatePublished - Aug 1 2007

Keywords

  • ASP
  • Drug secretion
  • Fluorescence imaging
  • Organic cation transport
  • Two-photon microscopy

ASJC Scopus subject areas

  • Nephrology

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