title: Novel orexigenic pathway prostaglandin D2-NPY system--involvement in orally active orexigenic δ opioid peptide.
abstract: Prostaglandin (PG) D(2), the most abundant PG in the central nervous system (CNS), is a bioactive lipid having various central actions including sleep induction, hypothermia and modulation of the pain response. We found that centrally administered PGD(2) stimulates food intake via the DP(1) among the two receptor subtypes for PGD(2) in mice. Hypothalamic mRNA expression of lipocalin-type PGD synthase (L-PGDS), which catalyzes production of PGD(2) from arachidonic acid via PGH(2) in the CNS, was increased after fasting. Central administration of antagonist and antisense ODN for the DP(1) receptor remarkably decreased food intake, body weight and fat mass. The orexigenic activity of PGD(2) was also blocked by an antagonist of Y(1) receptor for NPY, the most potent orexigenic peptide in the hypothalamus. Thus, the central PGD(2)-NPY system may play a critical role in food intake regulation under normal physiological conditions. We also found that orally active orexigenic peptide derived from food protein activates the PGD(2)-NPY system, downstream of δ opioid receptor. We revealed that the δ agonist peptide, rubiscolin-6-induced orexigenic activity was mediated by L-PGDS in the leptomeninges but not parenchyma using conditional knockout mice. In this review, we discuss the PGD(2)-NPY system itself, and orexigenic signals to activate it.
authors.affiliation: Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Gokasho Uji, Kyoto 611-0011, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Kaneko
authors.forename: Masaaki
authors.initials: M
authors.lastname: Yoshikawa
authors.forename: Kousaku
authors.initials: K
authors.lastname: Ohinata
mesh_terms: D000818:Animals; D001066:Appetite / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D054834:Lipocalins / Q000378:metabolism; D008578:Meninges / Q000187:drug effects; D009478:Neuropeptide Y / Q000494:pharmacology* / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology; D015230:Prostaglandin D2 / Q000494:pharmacology* / Q000502:physiology*; D011971:Receptors, Immunologic / Q000187:drug effects / Q000502:physiology; D017465:Receptors, Opioid, delta / Q000502:physiology*; D011982:Receptors, Prostaglandin / Q000187:drug effects / Q000502:physiology; D012273:Ribulose-Bisphosphate Carboxylase / Q000494:pharmacology
chemical_list: D054834:Lipocalins; D009478:Neuropeptide Y; D010446:Peptide Fragments; D011971:Receptors, Immunologic; D017465:Receptors, Opioid, delta; D011982:Receptors, Prostaglandin; C443993:rubiscolin 6; D012273:Ribulose-Bisphosphate Carboxylase; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase; D015230:Prostaglandin D2; C036293:prostaglandin D2 receptor