[Effect of L-DOPA on brain serotonin metabolism related to tryptophan concentrations in plasma and brain of rats].
Changes in tryptophan (Trp) concentrations in the peripheral and brain tissues and their influences on brain serotonin (5-HT) metabolism were investigated after i.p. administrations of L-DOPA alone and in combination with Ro4-4602 in male Wistar rats. L-DOPA alone elicited marked increases of both plasma free and liver Trp levels, and a slight increase of brain Trp level. Concomitant application of L-DOPA and Ro4-4602 did not change peripheral Trp concentrations but did reduce brain Trp level. Brain 5-HT levels were reduced in proportion to the increase of dopamine (DA) level by L-DOPA alone and Ro4-4602 plus L-DOPA. A marked increase of 5-HIAA level was exhibited by L-DOPA alone, while Ro4-4602 plus L-DOPA increased 5-HIAA levels slightly despite a marked decrease in 5-HT levels. The decrease of 5-HT and increase of 5-HIAA levels were also observed after administration of L-DOPA to neonatal rats in which the brain tryptophan hydroxylase was considered to be saturated. These results suggest that changes in 5-HT metabolism after L-DOPA injections are not only caused by DA which displaces 5-HT from vesicular stores, but also by changes in Trp concentrations in the plasma and brain which alter 5-HT synthesis and turnover.
D000818:Animals; D001545:Benserazide / Q000008:administration & dosage; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry / Q000187:drug effects; D004298:Dopamine / Q000008:administration & dosage / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007980:Levodopa / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism*; D014364:Tryptophan / Q000097:blood / Q000378:metabolism*
D012701:Serotonin; D007980:Levodopa; D006897:Hydroxyindoleacetic Acid; D001545:Benserazide; D014364:Tryptophan; D004298:Dopamine