title: High tryptophan diet reduces extracellular dopamine release via kynurenic acid production in rat striatum.
abstract: At endogenous brain concentrations, the neuroinhibitory tryptophan metabolite kynurenic acid (KYNA) is a preferential antagonist of the α7 nicotinic acetylcholine receptor (α7nAChR). In the present study, male Wistar rats were fed a high tryptophan diet (adding 0.1-1.5% tryptophan) for 24 h to examine (i) the effect of increased tryptophan on extracellular dopamine (DA) and KYNA levels and (ii) to determine any possible interactions between DA and KYNA. Brain KYNA levels were dose-dependently increased by tryptophan intake, and these increase were consistent with kynurenine (KYN), the precursor to KYNA, levels in the brain, plasma and liver. Administration of the 1.5% tryptophan added diet reduced the extracellular DA level to 60%, and increased the extracellular KYNA to 320% in the striatum. The DA reduction was attenuated through inhibiting KYNA synthesis with 2-aminoadipic acid. These results indicate that a high tryptophan diet can induce KYNA production and suppress DA release. One possible mechanism is that as more KYN is metabolized from the high doses of tryptophan in the liver and released into the blood stream, KYNA production in astrocytes is enhanced and the increased extracellular KYNA inhibits DA release by blocking α7nAChRs. Dietary manipulation of KYNA formation in astrocytes may offer a unique strategy to modulate DA.
authors.affiliation: Department of Food Science and Nutrition, School of Human Cultures, The University of Shiga Prefecture, Shiga, Japan.
authors.forename: Alato
authors.initials: A
authors.lastname: Okuno
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Fukuwatari
authors.forename: Katsumi
authors.initials: K
authors.lastname: Shibata
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects*; D004032:Diet; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000187:drug effects*; D006719:Homovanillic Acid / Q000378:metabolism; D066298:In Vitro Techniques; D007736:Kynurenic Acid / Q000378:metabolism*; D007737:Kynurenine / Q000378:metabolism; D008297:Male; D017551:Microdialysis / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D018709:Statistics, Nonparametric; D014364:Tryptophan / Q000008:administration & dosage*
chemical_list: D015102:3,4-Dihydroxyphenylacetic Acid; D007737:Kynurenine; D014364:Tryptophan; D007736:Kynurenic Acid; D004298:Dopamine; D006719:Homovanillic Acid