Identification of the Cationic Amino Acid Transporter (System y⁺) of the Rat Blood‐Brain Barrier

Abstract

Cationic amino acids are transported from blood into brain by a saturable carrier at the blood-brain barrier (BBB). The transport properties of this carrier were examined in the rat using an in situ brain perfusion technique. Influx into brain via this system was found to be sodium independent and followed Michaelis-Menten kinetics with half-saturation constants (Km) of 50-100 microM and maximal transport rates of 22-26 nmol/min/g for L-lysine, L-arginine, and L-ornithine. The kinetic properties matched that of System y+, the sodium-independent cationic amino acid transporter, the cDNA for which has been cloned from the mouse. To determine if the cloned receptor is expressed at the BBB, we assayed RNA from rat cerebral microvessels and choroid plexus for the presence of the cloned transporter mRNA by RNase protection. The mRNA was present in both cerebral microvessels and choroid plexus and was enriched in microvessels 38-fold as compared with whole brain. The results indicate that System y+ is present at the BBB and that its mRNA is more densely expressed at cerebral microvessels than in whole brain.

A New Member of the Cationic Amino Acid Transporter Family Is Preferentially Expressed in Adult Mouse Brain

“…In this context, the induced nitric oxide synthesis observed in brain astrocytes was reported to be partly dependent on induction of CAT2 (20). It has also been reported that cationic amino acid transport activity across the blood-brain barrier had the kinetic properties of system y ϩ and that CAT1 mRNA was 38-fold enriched in microvessels as compared with wholebrain (42).…”

Cationic amino acid transporter 1‐mediated l‐arginine transport at the inner blood–retinal barrier

“…The source of L-arginine in humans and most mammals is mostly renal de novo synthesis and dietary intake, and that of L-lysine, an essential amino acid, is exclusively by dietary intake, showing that L-arginine and L-lysine must be taken up by the retina from the circulating blood. CAT1 is reported to mediate the transport of cationic amino acids at the blood-brain barrier (Stoll et al 1993;O'Kane et al 2006), implying the similar roles of CAT1 in neural tissues. Accordingly, CAT1 in neural tissues such as retina and brain is physiologically essential for satisfying the neural requirements of L-arginine and L-lysine through its functional expression at the barrier-forming cells.…”

Multiple pathways for cationic amino acid transport in rat thyroid epithelial cell line PC Cl3

“…d RNase protection assay on RNA from rat cerebral microvessels to assess the presence of the transporter; transport assayed by in situ brain perfusion (39).…”