Functional relevance of carnitine transporter OCTN2 to brain distribution of L-carnitine and acetyl-L-carnitine across the blood-brain barrier

Transport of L-[H-3]carnitine and acetyl-L-[H-3]carnitine at the blood-brai n barrier (BBB) was examined by using in vivo and in vitro models. In vivo brain uptake of acetyl-L-[H-3]carnitine, determined by a rat brain perfusio n technique, was decreased in the presence of unlabeled acetyl-L-carnitine and in the absence of sodium ions. Similar transport properties for L-[H-3] carnitine and/or acetyl-L-[H-3]carnitine were observed in primary cultured brain capillary endothelial cells (BCECs) of rat, mouse, human, porcine and bovine, and immortalized rat BCECs, RBEC1. Uptakes of L-[H-3]carnitine and acetyl-L[H-3]carnitine by RBEC1 were sodium ion-dependent, saturable with K-m values of 33.1 +/- 11.4 mum and 31.3 +/- 11.6 mum, respectively, and in hibited by carnitine analogs. These transport properties are consistent wit h those of carnitine transport by OCTN2. OCTN2 was confirmed to be expresse d in rat and human BCECs by an RT-PCR method. Furthermore, the uptake of ac etyl-L-[H-3]carnitine by the BCECs of juvenile visceral steatosis (jvs) mou se, in which OCTN2 is functionally defective owing to a genetical missense mutation of one amino acid residue, was reduced. The brain distributions of L-[H-3]carnitine and acetyl-L-[H-3]carnitine in jvs mice were slightly low er than those of wild-type mice at 4 h after intravenous administration. Th ese results suggest that OCTN2 is involved in transport of L-carnitine and acetyl-L-carnitine from the circulating blood to the brain across the BBB.