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.
Ohnishi
S
S
Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Kyoto 606-8507, Japan.
Saito
H
H
Fukada
A
A
Inui
K I
KI
D000818:Animals; D002331:Carnitine / Q000378:metabolism* / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism*; D002412:Cations / Q000378:metabolism; D002460:Cell Line; D016764:Cell Polarity; D002509:Cephaloridine / Q000494:pharmacology; D002511:Cephalosporins / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D017136:Ion Transport / Q000187:drug effects; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000378:metabolism*; D007700:Kinetics; D011802:Quinidine / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism*; D013552:Swine; D019789:Tetraethylammonium / Q000378:metabolism*
D002352:Carrier Proteins; D002412:Cations; D002511:Cephalosporins; D004791:Enzyme Inhibitors; D019789:Tetraethylammonium; D002927:Cimetidine; D012964:Sodium; D011802:Quinidine; D002509:Cephaloridine; D002331:Carnitine