Increase of brain tryptophan and stimulation of serotonin synthesis by salicylate.

Abstract

Indirect evidence indicates that the rate‐limiting step in the synthesis of brain 5‐HT is the concentration of tryptophan in brain and not, as previously considered (Green and Sawyer, 1966), tryptophan hydroxylase. In fact this enzyme has a Km for its substrate much higher than the concentration of tryptophan normally present in the mammalian brain (Jequier, Lovenberg and Sjoerdsma, 1967; Jequier, Robinson, Lovesberg and Sjoerdsma, 1969; Mcgeer, Peters and Mcgeer, 1968). Tryptophan is the only amino acid circulating in plasma which is highly bound to serum proteins (Mcmenamy and Oncley, 1958). We have previously shown that the free fraction of serum tryptophan controls the concentration of brain tryptophan and, therefore, 5‐HT synthesis as well (Tagliamonte, Biggio and Gessa, 1971d; Gessa, Biggio and Tagliamonte, 1972). Salicylate has been shown to displace tryptophan from its protein binding in plasma and to raise the free tryptophan concentration (Mcarthur and Dawkins, 1969; Smith and Lakatos, 1971). These considerations prompted us to study the effect of salicylate on tryptophan concentrations and 5‐HT metabolism in brain.