Properties of carnitine transport in rat kidney cortex slices.
The properties of carnitine transport were studied in rat kidney cortex slices. Tissue:medium concentration gradients of 7.9 for L-[methyl-14C]carnitine were attained after 60-min incubation at 37 degrees C in 40 microM substrate. L- and D-carnitine uptake showed saturability. The concentration curves appeared to consist of (1) a high-affinity component, and (2) a lower affinity site. When corrected for the latter components, the estimated Km for L-carnitine was 90 microM and V = 22 nmol/min per ml intracellular fluid; for D-carnitine, Km = 166 microM and V = 15 nmol/min per ml intracellular fluid. The system was stereospecific for L-carnitine. The uptake of L-carnitine was inhibited by (1) D-carnitine, gamma-butyrobetaine, and (2) acetyl-L-carnitine. gamma-Butyrobetaine and acetyl-L-carnitine were competitive inhibitors of L-carnitine uptake. Carnitine transport was not significantly reduced by choline, betaine, lysine or gamma-aminobutyric acid. Carnitine uptake was inhibited by 2,4-dinitrophenol, carbonyl cyanide m-chlorophenyl-hydrazone, N2 atmosphere, KCN, N -ethylmaleimide, low temperature (4 degrees C) and ouabain. Complete replacement of Na+ in the medium by Li+ reduced L- and D-carnitine uptake by 75 and 60%, respectively. Complete replacement of K+ or Ca2+ in the medium also significantly reduces carnitien uptake. Two roles for the carnitine transport system in kidney are proposed: (1) a renal tubule reabsorption system for the steady-state maintenance of plasma carnitine; and (2) maintenance of normal carnitine levels in kidney cells, which is required for fatty acid oxidation.
D000108:Acetylcarnitine / Q000378:metabolism; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D001665:Binding Sites; D001693:Biological Transport, Active / Q000187:drug effects; D002331:Carnitine / Q000378:metabolism*; D066298:In Vitro Techniques; D007477:Ions; D007672:Kidney Cortex / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D051381:Rats; D013237:Stereoisomerism
D000963:Antimetabolites; D007477:Ions; D000108:Acetylcarnitine; D002331:Carnitine