title: Involvement of the long-chain fatty acid receptor GPR40 as a novel pain regulatory system.
abstract: G-protein receptor (GPR) 40 is known to be activated by docosahexaenoic acid (DHA). However, reports studying the role and functions (including pain regulation) of GPR40 in the brain are lacking. We investigated the involvement of GPR40 in the brain on DHA-induced antinociceptive effects. Expression of GPR40 protein was observed in the olfactory bulb, striatum, hippocampus, midbrain, hypothalamus, medulla oblongata, cerebellum and cerebral cortex in the brain as well as the spinal cord, whereas GPR120 protein expression in these areas was not observed. Intracerebroventricular (i.c.v.), but not intrathecal (i.t.) injection of DHA (25 and 50μg/mouse) and GW9508 (a GPR40- and GPR120-selective agonist; 0.1 and 1.0μg/mouse) significantly reduced formalin-induced pain behavior. These effects were inhibited by pretreatment with the μ opioid receptor antagonist β-funaltrexamine (β-FNA), naltrindole (δ opioid receptor antagonist) and anti-β-endorphin antiserum. The κ opioid receptor antagonist norbinaltorphimine (nor-BNI) did not affect the antinociception of DHA or GW9508. Furthermore, the immunoreactivity of β-endorphin in the hypothalamus increased at 10 and 20min after i.c.v. injection of DHA and GW9508. These findings suggest that DHA-induced antinociception via β-endorphin release may be mediated (at least in part) through GPR40 signaling in the supraspinal area, and may provide valuable information on a novel therapeutic approach for pain control.
authors.affiliation: Department of Clinical Pharmacy, Kobe Gakuin University, School of Pharmaceutical Sciences, 1-1-3 Minatojima, Chuo-ku, Kobe 650-8586, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Nakamoto
authors.forename: Takashi
authors.initials: T
authors.lastname: Nishinaka
authors.forename: Kengo
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Fumiyo
authors.initials: F
authors.lastname: Kasuya
authors.forename: Mitsumasa
authors.initials: M
authors.lastname: Mankura
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Koyama
authors.forename: Shogo
authors.initials: S
authors.lastname: Tokuyama
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000502:physiology*; D004281:Docosahexaenoic Acids / Q000502:physiology*; D004357:Drug Synergism; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007276:Injections, Intraventricular / Q000379:methods; D008297:Male; D008744:Methylamines / Q000494:pharmacology; D051379:Mice; D009292:Narcotic Antagonists / Q000494:pharmacology; D059408:Pain Management / Q000379:methods*; D010147:Pain Measurement; D011422:Propionates / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology; D001615:beta-Endorphin / Q000502:physiology
chemical_list: D000700:Analgesics; C473036:Ffar1 protein, mouse; C515630:GW9508; D008744:Methylamines; D009292:Narcotic Antagonists; D011422:Propionates; D043562:Receptors, G-Protein-Coupled; D011957:Receptors, Opioid; D004281:Docosahexaenoic Acids; D001615:beta-Endorphin