Interaction in the cerebral metabolism of the biogenic amines: effect of intravenous infusion of L-tryptophan on the metabolism of dopamine and 5-hydroxyindoles in brain and cerebrospinal fluid.

1. In dogs, an intravenous injection of L-tryptophan followed by intravenous infusion of L-tryptophan, although unable to maintain stable concentrations of tryptophan in the plasma or cerebrospinal fluid, produced stable, raised concentrations of 5-hydroxyindol-3-ylacetic acid (5-HIAA) in the cerebrospinal fluid (c.s.f.). This indicated that it was possible to raise the concentrations of the 5-hydroxyindoles in brain and to maintain the cerebral metabolism in a new steady state.2. The regional distribution of the total molal concentration of the 5-hydroxyindoles in brain after the administration of tryptophan was similar to the distribution found in control animals, thus suggesting the normal rate limiting step of metabolism, the activity of the enzyme tryptophan 5-hydroxylase, was still the controlling factor.3. Tryptophan administration caused a greater proportionate increase in the concentration of 5-HIAA than in that of 5-hydroxytryptamine (5-HT) in all regions of brain, perhaps indicating that the ;storage' capacity for 5-HT becomes filled under these conditions.4. Administration of tryptophan caused a large rise in the concentration of homovanillic acid in c.s.f. demonstrating that there was an interaction between the cerebral metabolism of tryptophan and dopamine.