Glutamate uptake is inhibited by L-arginine in mitochondria isolated from rat cerebrum

Uptake of L-[14C]glutamate (L-[14C]GLU) into nonsynaptic mitochondria isolated from rat cerebral hemispheres was measured in the presence of potential modulators of amino acid transport. The L-GLU carrier agonist 0.2 mM L-aspartate (L-ASP) virtually abolished L-GLU uptake (ASP/GLU concentration ratio, 1:1). L-Arginine (L-ARG) inhibited L-GLU uptake in a dose dependent manner over the concentration range 0.1-5 mM to maximum inhibition of 85%. Putrescine or ammonia had no effect, whereas 5 mM creatine and the NO generator, 5 mM sodium nitroprusside, increased the uptake by 73% and 57%, respectively. D-ARG was three times less effective in inhibiting L-GLU uptake than L-ARG at 5 mM concentration. The L-amino acids ornithine, lysine, histidine, tyrosine, phenylalanine, proline, leucine, isoleucine, tryptophan, glycine, methionine, valine, serine, taurine, alanine or cysteine did not affect the uptake when added in concentrations of 2-5 mM. A 14% inhibition of L-GLU uptake was noted in the presence of L-glutamine (L-GLN) (2 mM) or a dicarboxylate carrier ligand, alpha-ketoglutarate (alpha-KG) (5 mM), and a 30% inhibition with a dicarboxylate carrier inhibitor phenylsuccinate (PhSc) (5 mM). The results suggest that L-ARG functions as a specific endogenous modulator of cerebral mitochondrial L-GLU transport.