Amino acid assignment to one of three blood-brain barrier amino acid carriers

TLDR

The study quantified 14C‑labeled amino acid retention in rat brain 15 s after carotid injection, using 3HOH as a diffusible internal standard and [113mIn]EDTA to correct for incomplete washout, and demonstrated self‑ and cross‑inhibition with unlabeled amino acids and carboxylic acids. All tested amino acids except proline, alanine, and glycine were assigned to one of three distinct BBB carrier systems: a neutral carrier for phenylalanine, leucine, tyrosine, isoleucine, methionine, tryptophan, valine, DOPA, cysteine, histidine, threonine, glutamine, asparagine, and serine; a basic carrier for arginine, ornithine, and lysine; and a low‑capacity carrier for aspartic and glutamic acids.

Abstract

The percentages of 22 14C-labeled amino acids remaining in rat brain 15 s after carotid injection were measured relative to a simultaneously injected diffusible internal standard, 3HOH. The injected solution also contained a nondiffusible internal standard, [113mIn]EDTA to correct for incomplete brain blood compartment washout. Self-inhibition and cross-inhibition was demonstrated by inclusion of unlabeled amino acids and carboxylic acids. All amino acids tested, excluding proline, alanine, and glycine, could be assigned to one, and only one, blood-brain barrier carrier system. The neutral carrier system transported phenylalanine, leucine, tyrosine, isoleucine, methionine, tryptophane, valine, DOPA, cysteine, histidine, threonine, glutamine, asparagine, and serine. Affinity for a basic amino acid carrier system was demonstrated for arginine, ornithine, and lysine. A third, low-capacity independent carrier system transporting aspartic and glutamic acids was demonstrated.