Transport of L-tryptophan into slices of rat cerebral cortex

—Slices of rat cerebral cortex, when incubated aerobically at 37°C in Krebs-Ringer-phosphate solution (pH 7.0) containing 10 mm glucose and 1.0 mm l -tryptophan [1-¹⁴C], accumulated tryptophan. Within the first 15 min of incubation the ratio of the concentration of the amino acid in the tissue to that in the medium reached 3.5:1. Uptake of tryptophan was linear for the first 30 min and attained a maximum concentration ratio (tissue:medium) of 6.5:1 within 60 min. The transport mechanism became saturated at 1.0-3.0 mm tryptophan. Entry of the amino acid into the cortical cells was thereafter directly proportional to its initial concentration in the medium. The tissue: medium ratio at 15 min decreased significantly under the following experimental conditions: (1) lowering the incubation temperature to 0°C; (2) incubating under N₂; (3) omitting glucose; (4) decreasing the Na⁺ concentration below 50 mm ; (5) removing K⁺ from the medium; or (6) adding 1.0 mm NaCN or 0.1 mm protoveratrine B to the medium. These results provided evidence that the accumulation of tryptophan against its concentration gradient was an active process. The effects of a number of amino acids on the uptake of tryptophan were studied: of these, l -phenylalanine, dl -p-chlorophenylalanine, l -tyrosine, l -DOPA, the branched chain aliphatic amino acids (l -leucine, l -isoleucine, l -valine) and l -glutamic acid were found to be the most potent inhibitors of tryptophan transport. Several tryptophan metabolites were tested; only l -kynurenine inhibited the uptake of tryptophan.