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Indoleamine Metabolism in Rat Brain Studied Through Measurements of Tryptophan, 5‐Hydroxyindoleacetic Acid, and Indoleacetic Acid in Cerebrospinal Fluid

Tryptophan, 5‐hydroxyindoleacetic acid (5HIAA), and indoleacetic acid (IAA) were measured in rat cerebrospinal fluid (CSF) using high‐performance liquid chromatography with fluorometric detection in order to study brain indoleamine metabolism. Previously we have shown that IAA in CSF is derived from tryptamine in the CNS. In this study our results indicated that the synthesis of both 5‐hydroxytryptamine (5HT) and tryptamine varied with changes in brain tryptophan. After a tryptophan load, tryptamine synthesis increased much more than 5HT synthesis; under these circumstances, it can be of the same order of magnitude as 5HT synthesis. Studies with treatments that cause release of 5HT (reserpine and cold stress) indicated that tryptamine is not released with 5HT and is probably not stored in vesicles. Use of selective monoamine oxidase inhibitors suggested that results obtained in vitvo concerning the substrates for monoamine oxidase A and B apply in vivo. Thus, 5HT was acted on preferentially by the A enzyme, and tryptamine by the B enzyme. Measurement of IAA in brain, CSF, and plasma before and after probenecid indicated that there are active transport systems moving IAA from CSF and brain to blood, and from brain to CSF. Our data suggest that measurements of CSF IAA are a simple and convenient way of studying CNS tryptamine metabolism and should be applied clinically.