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

Department of Nephrology, School of Medicine, University Hospital, Essen, Germany.

Kidney international 2007 Aug

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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.

Citation

M Hörbelt, C Wotzlaw, T A Sutton, B A Molitoris, T Philipp, A Kribben, J Fandrey, F Pietruck. Organic cation transport in the rat kidney in vivo visualized by time-resolved two-photon microscopy. Kidney international. 2007 Aug;72(4):422-9