The uptake of carnitine by slices of rat cerebral cortex.
The properties of carnitine transport were studied in rat brain slices. A rapid uptake system for carnitine was observed, with tissue-medium gradients of 38 +/- 3 for L-[14CH3]carnitine and 27 +/- 3 for D-[14CH3]carnitine after 180 min incubation at 37 degrees C in 0.64 mM substrate. Uptake of L- and D-carnitine showed saturability. The estimated values of Km for L- and D-carnitine were 2.85 mM and 10.0 mM, respectively; but values of Vmax (1 mumol/min/ml intracellular fluid) were the same for the two isomers. The transport system showed stereospecificity for L-carnitine. Carnitine uptake was inhibited by structurally related compounds with a four-carbon backbone containing a terminal carboxyl group. L-Carnitine uptake was competitively inhibited by gamma-butyrobetaine (Ki = 3.22 mM), acetylcarnitine (Ki = 6.36 mM), and gamma-aminobutyric acid (Ki = 0.63 mM). The data suggest that carnitine and gamma-aminobutyric acid interact at a common carrier site. Transport was not significantly reduced by choline or lysine. Carnitine uptake was inhibited by an N2 atmosphere, 2,4-dinitrophenol, carbonylcyanide-N-chlorophenylhydrazone, potassium cyanide, n-ethylmaleimide, and ouabain. Transport was abolished by low temperature (4 degrees C) and absence of glucose from the medium. Carnitine uptake was Na+-dependent, but did not require K4+ or Ca2+.
D000818:Animals; D001692:Biological Transport; D002250:Carbon Radioisotopes; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D002331:Carnitine / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism*; D004140:Dinitrophenols / Q000494:pharmacology; D005033:Ethylmaleimide / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D010042:Ouabain / Q000494:pharmacology; D010100:Oxygen; D011190:Potassium Cyanide / Q000494:pharmacology; D051381:Rats
D002250:Carbon Radioisotopes; D004140:Dinitrophenols; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D010042:Ouabain; D011190:Potassium Cyanide; D005033:Ethylmaleimide; D002331:Carnitine; D010100:Oxygen