Blood-brain barrier controls carnitine level in the brain: a study on a model system with RBE4 cells.
Transport of carnitine was studied with immortalized rat brain endothelial cells (RBE4), an in vitro model of the blood-brain barrier. The experiments on uptake and efflux through the luminal membrane excluded any involvement of choline and amino acids transporters, as well as that of glycoprotein P. Acetyl-, octanoylcarnitine, and betaine were without any effect; the only compound decreasing both processes was butyrobetaine. An exposure of the abluminal membrane resulted in a 40% inhibition of carnitine uptake by the substrates of neutral amino acid transporter L, while its efflux through the basolateral membrane, occurring in a form of free carnitine, was sensitive to SH group reagent, mersalyl, and was diminished by butyrobetaine. These features of carnitine transport did not fully correspond to the known characteristics of the proteins transporting carnitine in other tissues (OCTN2 and CT1); however, they did not exclude an involvement of a transporter belonging to the same superfamily. Moreover, such a protein in brain endothelium would fulfill a regulatory role in the transport of carnitine through the blood-brain barrier.
Mroczkowska
J E
JE
Nencki Institute of Experimental Biology, 3 Pasteur Street, Warsaw, 02-093, Poland.
Roux
F S
FS
Naleçz
M J
MJ
Naleçz
K A
KA
D000108:Acetylcarnitine / Q000494:pharmacology; D000818:Animals; D001622:Betaine / Q000494:pharmacology; D001812:Blood-Brain Barrier / Q000502:physiology*; D001921:Brain / Q000378:metabolism*; D002331:Carnitine / Q000031:analogs & derivatives / Q000494:pharmacology; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002560:Cerebrovascular Circulation; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008833:Microcirculation; D008954:Models, Biological; D051381:Rats
D001622:Betaine; D000108:Acetylcarnitine; C008698:octanoylcarnitine; D002331:Carnitine