Sodium gradient-stimulated transport of L-carnitine into renal brush border membrane vesicles: kinetics, specificity, and regulation by dietary carnitine.
L-Carnitine transport by rat renal brush border membrane vesicles was stimulated by a Na+ gradient (extravesicular greater than intravesicular). Total carnitine entry was 2.7 and 3.2 times higher at 15 S in the presence of a 100 mM NaCl gradient than when the vesicles were incubated isoosmotically in buffered 100 mM KCl or buffered mannitol, respectively. Specific carnitine transport (total entry minus contribution from diffusion) was stimulated 3.6- and 5.7-fold, respectively. An "overshoot" was observed for total carnitine entry in the presence of a Na+ gradient but not in the presence of a K+ gradient or in the absence of an ion gradient. L-Carnitine transport was saturable. KT and Vmax for total carnitine transport were 0.11 mM and 11.6 pmol S-1 mg protein-1, respectively, and for Na+-gradient-dependent carnitine transport, 0.055 mM and 5.09 pmol S-1 mg protein-1, respectively. The transport process was structure-specific for a quaternary nitrogen and carboxyl groups attached by a 4- to 6-carbon chain, but without other charged functional groups. Other evidence for a carrier-mediated process included trans-stimulation of transport by intravesicular carnitine and a peak of activity at near physiological temperature. Kinetic data derived from this study, coupled with data from previous physiological studies from this laboratory, suggests that carnitine transport by the brush border membrane is not limiting for carnitine reabsorption. Dietary carnitine (1% of diet for 10 days) reduced by 52% the rate of carnitine transport across the brush border membrane in vitro, without affecting rates of D-glucose, L-lysine, L-glutamic acid, or L-alanine transport. Down-regulation of carnitine transport may prevent excessive or toxic accumulation of L-carnitine in renal tubular cells exposed to high extracellular carnitine concentrations.
D000818:Animals; D001692:Biological Transport; D002331:Carnitine / Q000378:metabolism* / Q000494:pharmacology; D004032:Diet; D005947:Glucose / Q000378:metabolism; D066298:In Vitro Techniques; D007668:Kidney / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008871:Microvilli / Q000378:metabolism; D051381:Rats; D012964:Sodium / Q000502:physiology*; D013696:Temperature
D012964:Sodium; D005947:Glucose; D002331:Carnitine