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—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.

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SYNOPSIS Tryptophan was measured in the ventricular CSF and serum, and the neutral amino acids leucine, isoleucine, valine, phenylalanine, and tyrosine were measured in the serum of two cases with ventricular drains. Samples were taken every two hours for 24 hours in one case and for 16 hours in the other. The CSF tryptophan was correlated significantly with the free-that is, nonalbumin-bound-serum tryptophan but not with the total serum tryptophan. CSF tryptophan was not correlated significantly with the ratio of free serum tryptophan to the sum of the neutral amino acids. These data suggest that, in man, brain tryptophan concentrations are influenced by the free and not the total serum tryptophan and that physiological variations of the neutral amino acids do not appreciably influence the concentration of brain tryptophan.