Independent organic cation transport activity of Na(+)-L-carnitine cotransport system in LLC-PK(1) cells.

We investigated expression of the Na(+)-L-carnitine cotransport system and its role in transport of tetraethylammonium in a kidney epithelial cell line, LLC-PK(1). L-Carnitine uptake in the LLC-PK(1) cells was markedly stimulated in the presence of Na(+). The uptake was saturable, with Michaelis constant and maximal uptake velocity values of 7.8 microM and 153.7 pmol x mg protein(-1) x 15 min(-1), respectively. Cationic drugs such as tetraethylammonium, cimetidine, and quinidine inhibited L-carnitine uptake. The basolateral-to-apical transport of [(14)C]tetraethylammonium was enhanced markedly in the presence of an H(+) gradient on the apical side at a pH of 5.9. Under the conditions in which Na(+)/L-carnitine cotransport activity was saturable by the addition of 100 microM L-carnitine to the apical-side medium, the basolateral-to-apical transcellular transport of [(14)C]tetraethylammonium was unaffected. These results suggested that the Na(+)-L-carnitine cotransporter is expressed in the apical membranes of LLC-PK(1) cells, and is not responsible for efflux of tetraethylammonium from the cells. Transport of tetraethylammonium appeared to be mediated predominantly by an H(+)/organic cation antiporter in the apical membranes.