Uptake of acetyl-L-carnitine in the brain.
Analysis in mouse brain slices of the uptake of acetyl-L-[N-methyl-14C]carnitine with time showed it to be concentrative, and kinetic analysis gave a Km of 1.92 mM and a Vmax of 1.96 mumol/min per ml, indicating the presence of a low-affinity carrier system. The uptake was energy-requiring and sodium-dependent, being inhibited in the presence of nitrogen (absence of O2), sodium cyanide, low temperature (4 degrees C), and ouabain, and in the absence of Na+. The uptake of acetyl-L-carnitine was not strictly substrate-specific; gamma-butyrobetaine, L-carnitine, L-DABA, and GABA were potent inhibitors, hypotaurine and L-glutamate were moderate inhibitors, and glycine and beta-alanine were only weakly inhibitory. In vivo, acetyl-L-carnitine transport across the blood-brain barrier had a brain uptake index of 2.4 +/- 0.2, which was similar to that of GABA. These results indicate an affinity of acetyl-L-carnitine to the GABA transport system.
Burlina
A P
AP
Nathan S. Kline Institute for Psychiatric Research, Center for Neurochemistry, New York, NY 10035.
Sershen
H
H
Debler
E A
EA
Lajtha
A
A
D000108:Acetylcarnitine / Q000493:pharmacokinetics*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002331:Carnitine / Q000031:analogs & derivatives*; D005260:Female; D066298:In Vitro Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D005680:gamma-Aminobutyric Acid; D000108:Acetylcarnitine; D002331:Carnitine