The relation between urinary 5-hydroxyindoleacetic acid levels and the ratio of tryptophan to other large neutral amino acids placed in the stomach.

We assayed 5-hydroxyindoleacetic acid (5-HIAA) in urine samples (3- or 6 1/2-hr collection) after individual rats received 6-8 ml of water, of amino acids in solution, or of glucose by stomach tube. Tryptophan (Trp) solutions caused dose-related increases in urinary 5-HIAA; these were blocked when animals received carbidopa, an inhibitor of peripheral aromatic amino acid decarboxylase. The concurrent administration of a large neutral amino acid (LNAA; valine or isoleucine) with oral Trp, in high doses probably sufficient to compete with Trp for transport into gut cells, blocked the Trp-induced rise in urinary 5-HIAA. Concurrent administration of glycine (not a LNAA) in equivalent doses did not. Pretreatment with pyridoxine blocked the Trp-induced rise in urinary 5-HIAA but not that in brain serotonin (5-hydroxytryptamine, 5HT). These observations confirm the previous suggestion that while brain serotonin synthesis depends on the plasma Trp/LNAA ratio (which varies inversely with the proportion of protein to total calories in the diet), gut serotonin synthesis depends largely on the Trp/LNAA ratio in the dietary protein itself (and, probably, within the gut lumen postprandially). The range of molar Trp/LNAA ratios at which free LNAAs significantly diminish the effects of ingested Trp on gut serotonin synthesis (as reflected by urinary 5-HIAA) is similar to the range found in dietary proteins.