期刊
KIDNEY INTERNATIONAL
卷 72, 期 4, 页码 422-429出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.ki.5002317
关键词
drug secretion; organic cation transport; fluorescence imaging; two-photon microscopy; ASP(+)
资金
- NIDDK NIH HHS [R01 DK077124, DK-60621, P01 DK-53465, P50 DK-61594, R01 DK077124-01A1] Funding Source: Medline
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.
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