title: NERP-2 regulates gastric acid secretion and gastric emptying via the orexin pathway.
abstract: Neuroendocrine regulatory peptide (NERP)-2 is derived from a distinct region of VGF, a neurosecretory protein originally identified as a product of a nerve growth factor-responsive gene in rat PC12 cells. Colocalization of NERP-2 with orexin-A in the lateral hypothalamus increases orexin-A-induced feeding and energy expenditure in both rats and mice. Orexigenic and anorectic peptides in the hypothalamus modulate gastric function. In this study, we investigated the effect of NERP-2 on gastric function in rats. Intracerebroventricular administration of NERP-2 to rats increased gastric acid secretion and gastric emptying, whereas peripheral administration did not affect gastric function. NERP-2-induced gastric acid secretion and gastric emptying were blocked by an orexin 1 receptor antagonist, SB334867. NERP-2 also induced Fos expression in the lateral hypothalamus and the dorsomotor nucleus of the vagus X, which are key sites in the central nervous system for regulation of gastric function. Atropine, a blocker of vagal efferent signal transduction, completely blocked NERP-2-induced gastric acid secretion. These results demonstrate that central administration of NERP-2 activates the orexin pathway, resulting in elevated gastric acid secretion and gastric emptying.
authors.affiliation: Neurology, Respirology, Endocrinology, and Metabolism, Division of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
authors.forename: Cherl
authors.initials: C
authors.lastname: Namkoong
authors.affiliation: Neurology, Respirology, Endocrinology, and Metabolism, Division of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan; Department of Sports and Fitness, Faculty of Wellness, Shigakkan University, Aichi, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Toshinai
authors.affiliation: Neurology, Respirology, Endocrinology, and Metabolism, Division of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
authors.forename: T M Zaved
authors.initials: TMZ
authors.lastname: Waise
authors.affiliation: Neurology, Respirology, Endocrinology, and Metabolism, Division of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Sakoda
authors.affiliation: Department of Pharmacology, National Cardiovascular Center Research Institute, Osaka, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Sasaki
authors.affiliation: Department of Physiology, School of Medicine, University of Occupational and Environmental Health, Fukuoka, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Ueta
authors.affiliation: Division of Endocrine and Metabolism, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
authors.forename: Min-Seon
authors.initials: MS
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, National Cardiovascular Center Research Institute, Osaka, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Minamino
authors.affiliation: Neurology, Respirology, Endocrinology, and Metabolism, Division of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan. Electronic address: nakazoto@med.miyazaki-u.ac.jp.
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Nakazato
mesh_terms: D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001583:Benzoxazoles / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism*; D005746:Gastric Emptying / Q000187:drug effects*; D007276:Injections, Intraventricular; D008297:Male; D009287:Naphthyridines; D009419:Nerve Tissue Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D064446:Orexin Receptors / Q000378:metabolism*; D010276:Parasympatholytics / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects*; D014508:Urea / Q000031:analogs & derivatives / Q000494:pharmacology; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology
chemical_list: C420062:1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea; D001583:Benzoxazoles; D009287:Naphthyridines; D009419:Nerve Tissue Proteins; D064446:Orexin Receptors; D010276:Parasympatholytics; C523896:neuroendocrine regulatory peptide-2, rat; D001285:Atropine; D014508:Urea
keywords: Gastric acid secretion; Gastric emptying; Neuroendocrine regulatory peptide-2 (NERP-2); Orexin; Vagal efferent activity