Whole-body Autoradiographic Studies on the Distribution of 14C-Labeled D-and L-5-Hydroxytryptophan, 5-Hydroxytryptamine and 5-Hydroxyindole-3-acetic Acid in Rats

The distribution of D-and L-isomers of 14C-labeled 5-hydroxytryptophan (5-HTP) was comparatively investigated by means of whole-body autoradiography following intravenous and oral administration to rats. The distribution of 14C-labeled 5-hydroxytryptamine (5-HT, serotonine) and 5-hydroxyindole-3-acetic acid (5-HIAA), the main end product of 5-HTP metabolism, was also studied for comparison purposes. The following differences were found in the distribution pattern of radioactivity between D-and L-isomers of 5-HTP : i) a rapid and appreciable uptake of radioactivity in the brain only by L-5-HTP, but none by D-5-HTP and 5-HT, ii) a high uptake and accumulation of radioactivity in the adrenal medulla by L-5-HTP and 5-HT, but none by D-5-HTP, iii) a high distribution of radioactivity in the skeletal muscle by L-5-HTP, but none by D-5-HTP and 5-HT, iv) a gradual accumulation of radioactivity in the spleen by L-5-HTP and 5-HT, but none by D-5-HTP, v) a high accumulation and retention in the pancreas by both D- and L-5-HTP, but none by 5-HT, and vi) a high absorbability of L-5-HTP from the intestine in contrast to a very limited absorbability of the D-isomer. The distribution pattern, particularly in regard to the brain uptake, of L-5-HTP-14C did not change substantially upon increasing the oral dosage, in contrast to a significant change observed for L-DOPA. 5-HIAA, when injected intravenously, was found to be eliminated from the body extremely rapidly through the urinary route. These results were discussed with respect to the possible use of L-5-HTP orally as a brain serotonine precursor.