Distinct transport activity of tetraethylammonium from L-carnitine in rat renal brush-border membranes.
We investigated the contribution of the Na(+)/L-carnitine cotransporter in the transport of tetraethylammonium (TEA) by rat renal brush-border membrane vesicles. The transient uphill transport of L-carnitine was observed in the presence of a Na(+) gradient. The uptake of L-carnitine was of high affinity (K(m)=21 microM) and pH dependent. Various compounds such as TEA, cephaloridine, and p-chloromercuribenzene sulfonate (PCMBS) had potent inhibitory effects for L-carnitine uptake. Therefore, we confirmed the Na(+)/L-carnitine cotransport activity in rat renal brush-border membranes. Levofloxacin and PCMBS showed different inhibitory effects for TEA and L-carnitine uptake. The presence of an outward H(+) gradient induced a marked stimulation of TEA uptake, whereas it induced no stimulation of L-carnitine uptake. Furthermore, unlabeled TEA preloaded in the vesicles markedly enhanced [14C]TEA uptake, but unlabeled L-carnitine did not stimulate [14C]TEA uptake. These results suggest that transport of TEA across brush-border membranes is independent of the Na(+)/L-carnitine cotransport activity, and organic cation secretion across brush-border membranes is predominantly mediated by the H(+)/organic cation antiporter.
Ohnishi
Shuichi
S
Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan.
Saito
Hideyuki
H
Fukada
Atsuko
A
Inui
Ken-ichi
K
D002731:4-Chloromercuribenzenesulfonate / Q000494:pharmacology; D000818:Animals; D001693:Biological Transport, Active; D002331:Carnitine / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007668:Kidney / Q000378:metabolism*; D064704:Levofloxacin; D008297:Male; D008871:Microvilli / Q000378:metabolism; D015242:Ofloxacin / Q000494:pharmacology; D027701:Organic Cation Transport Proteins / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013439:Sulfhydryl Reagents / Q000494:pharmacology; D019789:Tetraethylammonium / Q000037:antagonists & inhibitors / Q000378:metabolism*
D027701:Organic Cation Transport Proteins; D013439:Sulfhydryl Reagents; D002731:4-Chloromercuribenzenesulfonate; D019789:Tetraethylammonium; D064704:Levofloxacin; D015242:Ofloxacin; D002331:Carnitine