TRANSPORT OF l‐TRYPTOPHAN INTO SLICES OF RAT CEREBRAL CORTEX¹

Abstract

—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.

Effect of Aminophylline on Tryptophan and Other Aromatic Amino Acids in Plasma, Brain and Other Tissues and on Brain 5‐hydroxytryptamine Metabolism

“…(b) Competition between tryptophan and a group of neutral amino acids for uptake by the brain This has been shown in vitro (Kiely & Sourkes, 1972) and in vivo (Oldendorf, 1971). The tryptophan concentrations used in these experiments were considerably greater than those of free tryptophan in plasma.…”

Liver and Brain Tryptophan Metabolism Following Hydrocortisone Administration to Rats and Gerbils

“…This is probably because it competes with tryptophan for uptake into the brain, since kynurenine decreases accumulation of labelled tryptophan in brain slices Kiely & Sourkes, 1972) and decreases rat brain tryptophan 1 h following injection. Thus the finding that this compound had no effect on brain tryptophan concentrations and did not decrease brain 5-HT or 5-HIAA concentrations in the gerbil again indicates differences in tryptophan metabolism between these two rodents.…”

Metabolism of an oral tryptophan load. I: Effects of dose and pretreatment with tryptophan.

“…The high plasma kynurenine concentration attained during chronic tryptophan treatment is of particular interest as Green & Curzon (1970) and Kiely & Sourkes (1972) both found that kynurenine interfered with tryptophan transport into rat brain. The experiments of Gal et al (1978) in the rat suggest that the plasma concentrations observed in the current study might well cause a lowering of the amount of tryptophan transported into the brain.…”