Mechanism of Intestinal Absorption and Brain Uptake of l-5-Hydroxytryptophan in Rats, as compared to Those of L-3, 4-Dihydroxyphenylalanine

Abstract

L-5-Hydroxytryptophan (5-HTP) and L-3, 4-dihydroxyphenylalanine (DOPA) were comparatively investigated of their mechanisms of intestinal absorption, metabolism in the intestine and liver tissues and mechanisms of passage through the blood-brain barriers, by means of in vitro and/or in situ techniques using rat tissues. The corre-sponding D-isomers were also investigated for comparison. l-5-HTP, but not the d-isomer, was found to be absorbed from the intestine by an active transport mechanism in the same way as L-DOPA. In vitro studies using rat brain cortex slices proved that both l-5-HTP and l-dopa, but not their D-isomers, are taken up by the brain tissues by an active transport mechanism which is saturable, energy-dependent and competitive. There was no substantial difference between l-5-HTP and l-dopa in the rate of intestinal absorption and that of brain uptake. It was indicated, however, that L-5-HTP was decarboxylated in the intestine to a much less extent than l-dopa during the absorption and the decarboxylation activity of rat intestine and liver homogenates was found to be about four and seven times higher for l-dopa than for l-5-HTP, respectively. The latter results suggest that the oral dose of l-5-HTP can be much more easily transferred into the circulating blood without being suffered from decarboxylation in the peripheral organs than l-dopa, resulting in a more efficient penetration of l-5-HTP into the brain as a serotonine precursor. © 1977, The Pharmaceutical Society of Japan. All rights reserved.