title: Rubiscolin-6, a delta opioid peptide derived from spinach Rubisco, has anxiolytic effect via activating sigma1 and dopamine D1 receptors.
abstract: Rubiscolin-6 (Tyr-Pro-Leu-Asp-Leu-Phe) is a delta opioid peptide derived from the large subunit of spinach d-ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco). We previously reported that rubiscolin-6 had an analgesic effect and stimulated memory consolidation. Here we show that intraperitoneally (i.p.) or orally administered rubiscolin-6 has an anxiolytic effect at a dose of 10 mg/kg or 100 mg/kg, respectively, in the elevated plus-maze test in mice. The anxiolytic effects of rubscolin-6 after i.p. (10 mg/kg) and oral (100 mg/kg) administration were blocked by a delta opioid receptor antagonist, naltrindole (1 mg/kg, s.c.), suggesting that the anxiolytic activity of rubiscolin-6 is mediated by delta opioid receptor. The anxiolytic effect of rubiscolin-6 (10 mg/kg, i.p.) was also blocked by a dopamine D(1) antagonist, SCH23390 (30 microg/kg, i.p.), but not by a dopamine D(2) antagonist, raclopride (15 microg/kg, i.p.). The anxiolytic effect of rubiscolin-6 (10 mg/kg, i.p.) was blocked by sigma(1) receptor antagonist, BMY14802 (0.5 mg/kg, i.p.) or BD1047 (10 mg/kg, i.p.). Taken together, the anxiolytic effect of rubiscolin-6 is mediated by sigma(1) and dopamine D(1) receptors downstream of delta opioid receptor.
authors.affiliation: Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Hirata
authors.forename: Soushi
authors.initials: S
authors.lastname: Sonoda
authors.forename: Shun
authors.initials: S
authors.lastname: Agui
authors.forename: Mariko
authors.initials: M
authors.lastname: Yoshida
authors.forename: Kousaku
authors.initials: K
authors.lastname: Ohinata
authors.forename: Masaaki
authors.initials: M
authors.lastname: Yoshikawa
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010446:Peptide Fragments / Q000494:pharmacology*; D017447:Receptors, Dopamine D1 / Q000187:drug effects*; D017480:Receptors, sigma / Q000187:drug effects*; D012273:Ribulose-Bisphosphate Carboxylase / Q000494:pharmacology*; D000097605:Sigma-1 Receptor
chemical_list: D014151:Anti-Anxiety Agents; D010446:Peptide Fragments; D017447:Receptors, Dopamine D1; D017480:Receptors, sigma; D012273:Ribulose-Bisphosphate Carboxylase; D000097605:Sigma-1 Receptor; C443993:rubiscolin 6