Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Glube, N. et al.

OCTN2-Mediated Carnitine Uptake in a Newly Discovered Human Proximal Tubule Cell Line (Caki-1).

The proximal tubular reabsorption of carnitine in the human kidney is significant because more than 95% of the carnitine filtered in the kidney is reabsorbed by the proximal tubules therefore maintaining the homeostatic balance of carnitine in the body. Objectives of this study include the characterization of OCTN2 function in the Caki-1 cell line and the potential interactions of carnitine uptake with renally secreted drugs, including drugs of quaternary ammonium structure. Caki-1 cells were additionally characterized to be of proximal tubule nature, and an apical membrane expression pattern of OCTN2 in Caki-1 cells was discovered. Uptake studies with radiolabeled l-carnitine in Caki-1 cells revealed a Na+- and temperature-dependent carrier-mediated process (Km = 15.90 muM) which was unaffected by pH in a range from 6.5 to 8. 5. All drugs tested were able to inhibit the carnitine uptake process to different degrees. The quaternary ammonium compounds ciclotropium bromide and ipratropium bromide were strong inhibitors with IC50 values of 30 muM and 95 muM, respectively. The observed kinetics, immunohistolocalization, and inhibition studies indicate that the high-affinity uptake of carnitine in the Caki-1 cell line is most likely mediated by OCTN2. The interaction of drugs at the renal level with OCTN2 indicates a possible pathway for the final step of cationic secretion into the urine. Keywords: OCTN2; l-carnitine; proximal tubule; Caki-1; renal secretion.[1]

References

OCTN2-Mediated Carnitine Uptake in a Newly Discovered Human Proximal Tubule Cell Line (Caki-1). Glube, N., Closs, E., Langguth, P. Mol. Pharm. (2007) [Pubmed]

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