Serotonin synthesis and release in brain slices: independence of tryptophan

The purpose of the present study was to examine the role of substrate availability in the regulation of the release and synthesis of serotonin by brain slices. Electrical field depolarization of the brain slices stimulated the synthesis and release of serotonin in the absence of changes in intracellular tryptophan concentration, in the absence of tryptophan in the incubation bath, and in the absence of changes in total tryptophan uptake. Furthermore, electrical stimulation decreased the apparent Km for tryptophan required for synthesis of serotonin by the slices. Several conclusions were drawn. (1) Rates of serotonin release and synthesis in brain slices may increase independently of the tissue tryptophan concentration or tryptophan uptake. (2) There is little difference in the synthetic rate of serotonin in tissues exposed to pargyline or not at all. (3) Blockade of monoamine oxidase by pargyline appears to give estimates of the synthetic rates of serotonin which are comparable to estimates derived from [3H]-tryptophan incorporation. (4) Newly synthesized serotinin is preferentially released. (5) Only in tissue pretreated with pargyline do increasing concentrations of tryptophan increase the releasable pool of 5-HT. (6) Electrical depolarization may allosterically activate tryptophan hydroxylase; an effect which may be mimicked by homogenization of the tissue.