title: Inhibition of ghrelin-induced feeding in rats by pretreatment with a novel dual orexin receptor antagonist.
abstract: Orexin-A and -B, and ghrelin are potent orexigenic peptides. The effects of ACT462206, a novel dual orexin receptor antagonist (DORA), on ghrelin-induced feeding were examined in adult male Wistar rats. Hyperphagia induced by the intracerebroventricular (icv) administration of ghrelin was significantly suppressed for at least 2 h by pretreatment with icv administration of DORA. A marked increase was observed in the number of neurons showing Fos immunoreactivity in the paraventricular nucleus, arcuate nucleus and lateral hypothalamic area (LHA), 90 min after icv administration of ghrelin. Pretreatment with DORA significantly decreased the number of Fos-immunoreactive (IR) neurons; however, Fos immunoreactivity remained significantly increased. Double-immunostaining for Fos and orexin-A showed that many orexin-A-IR neurons in the LHA coexisted with Fos immunoreactivity after icv administration of ghrelin, but their number was reduced significantly by DORA pretreatment. These results suggest that centrally administered ghrelin may activate the orexinergic and non-orexinergic pathways responsible for the regulation of feeding.
authors.affiliation: Department of Health and Nutritional Care, Faculty of Medical Science, University of East Asia, Shimonoseki, 751-0807, Japan.|Department of Physiology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: So
authors.affiliation: Department of Physiology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Hashimoto
authors.affiliation: Department of Physiology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan.|Department of Pediatrics, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan.
authors.forename: Reiko
authors.initials: R
authors.lastname: Saito
authors.affiliation: Department of Pediatrics, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan.
authors.forename: Yukiyo
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Department of Physiology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan.
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Motojima
authors.affiliation: Department of Physiology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan.
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Ueno
authors.affiliation: Department of Physiology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan.
authors.forename: Satomi
authors.initials: S
authors.lastname: Sonoda
authors.affiliation: Department of Physiology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Yoshimura
authors.affiliation: Department of Physiology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Maruyama
authors.affiliation: Department of Pediatrics, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Kusuhara
authors.affiliation: Department of Physiology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan. yoichi@med.uoeh-u.ac.jp.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Ueta
mesh_terms: D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects / Q000378:metabolism; D004435:Eating / Q000187:drug effects*; D054439:Ghrelin / Q000494:pharmacology*; D007026:Hypothalamic Area, Lateral / Q000187:drug effects; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009479:Neuropeptides / Q000494:pharmacology; D000068796:Orexin Receptor Antagonists / Q000494:pharmacology*; D000068797:Orexins / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D054439:Ghrelin; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068796:Orexin Receptor Antagonists; D000068797:Orexins; D016760:Proto-Oncogene Proteins c-fos
keywords: Food intake; Fos; Ghrelin; Immunohistochemistry; Orexin receptor antagonist