title: β-Lactotensin derived from bovine β-lactoglobulin exhibits anxiolytic-like activity as an agonist for neurotensin NTS(2)  receptor via activation of dopamine D(1)  receptor in mice.
abstract: β-Lactotensin (His-Ile-Arg-Leu) is a bioactive peptide derived from bovine milk β-lactoglobulin, acting as a natural agonist for neurotensin receptors. We found that β-lactotensin exhibited anxiolytic-like activity in an elevated plus-maze test after its intraperitoneal (i.p.) administration in mice. β-Lactotensin was also orally active. The anxiolytic-like activity of β-lactotensin after i.p. administration was blocked by levocabastine, an antagonist for the neurotensin NTS(2) receptor. β-Lactotensin had anxiolytic-like activity in wild-type but not Ntsr2-knockout mice. β-Lactotensin increased intracellular Ca(2+) flux in glial cells derived from wild-type mice but not Ntsr2 knockout mice. These results suggest that β-lactotensin acts as an NTS(2) receptor agonist having anxiolytic-like activity. The anxiolytic-like activity of β-lactotensin was also blocked by SCH23390 and SKF83566, antagonists for dopamine D(1) receptor, but not by raclopride, an antagonist for D(2) receptor. Taken together, β-lactotensin may exhibit anxiolytic-like activity via NTS(2) receptor followed by D(1) receptor.
authors: Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Gokasho Uji, Kyoto, Japan.
authors: I-Ching
authors: IC
authors: Hou
authors: Chihiro
authors: C
authors: Suzuki
authors: Norimasa
authors: N
authors: Kanegawa
authors: Ayako
authors: A
authors: Oda
authors: Ayako
authors: A
authors: Yamada
authors: Masaaki
authors: M
authors: Yoshikawa
authors: Daisuke
authors: D
authors: Yamada
authors: Masayuki
authors: M
authors: Sekiguchi
authors: Etsuko
authors: E
authors: Wada
authors: Keiji
authors: K
authors: Wada
authors: Kousaku
authors: K
authors: Ohinata
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage*; D001253:Astrocytes / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004333:Drug Administration Routes; D004347:Drug Interactions; D005106:Exploratory Behavior / Q000187:drug effects; D018698:Glutamic Acid / Q000494:pharmacology; D007782:Lactoglobulins / Q000737:chemistry*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009842:Oligopeptides / Q000008:administration & dosage*; D010880:Piperidines / Q000494:pharmacology; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D018028:Receptors, Neurotensin / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000378:metabolism*; D013997:Time Factors
chemical_list: D014151:Anti-Anxiety Agents; D018492:Dopamine Antagonists; D007782:Lactoglobulins; C490984:Ntsr2 protein, mouse; D009842:Oligopeptides; D010880:Piperidines; D017448:Receptors, Dopamine D2; D018028:Receptors, Neurotensin; C064259:beta-lactoglobin W; C102984:beta-lactotensin; D018698:Glutamic Acid; C047340:levocabastine; D002118:Calcium