title: Dipeptide Tyr-Leu (YL) exhibits anxiolytic-like activity after oral administration via activating serotonin 5-HT1A, dopamine D1 and GABAA receptors in mice.
abstract: We found that Tyr-Leu (YL) dose-dependently exhibits potent anxiolytic-like activity (0.1-1mg/kg, i.p.) comparable to diazepam in the elevated plus-maze test in mice. YL was orally active (0.3-3mg/kg). A retro-sequence peptide or a mixture of Tyr and Leu was inactive. The anxiolytic-like activity of YL was inhibited by antagonists for serotonin 5-HT(1A), dopamine D(1) and GABA(A) receptors; however, YL had no affinity for them. We also determined the order of their activation is 5-HT(1A), D(1) and GABA(A) receptors using selective agonists and antagonists. Taken together, YL may exhibit anxiolytic-like activity via activation of 5-HT(1A), D(1) and GABA(A) receptors.
authors.affiliation: Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Gokasho Uji, Kyoto, Japan.
authors.forename: Norimasa
authors.initials: N
authors.lastname: Kanegawa
authors.forename: Chihiro
authors.initials: C
authors.lastname: Suzuki
authors.forename: Kousaku
authors.initials: K
authors.lastname: Ohinata
mesh_terms: D000284:Administration, Oral; D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004151:Dipeptides / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000378:metabolism*
chemical_list: D014151:Anti-Anxiety Agents; D004151:Dipeptides; D017447:Receptors, Dopamine D1; D011963:Receptors, GABA-A; D044282:Receptor, Serotonin, 5-HT1A; C031703:tyrosylleucine