title: Motilin Stimulates Gastric Acid Secretion in Coordination with Ghrelin in Suncus murinus.
abstract: Motilin and ghrelin constitute a peptide family, and these hormones are important for the regulation of gastrointestinal motility. In this study, we examined the effect of motilin and ghrelin on gastric acid secretion in anesthetized suncus (house musk shrew, Suncus murinus), a ghrelin- and motilin-producing mammal. We first established a gastric lumen-perfusion system in the suncus and confirmed that intravenous (i.v.) administration of histamine (1 mg/kg body weight) stimulated acid secretion. Motilin (0.1, 1.0, and 10 μg/kg BW) stimulated the acid output in a dose-dependent manner in suncus, whereas ghrelin (0.1, 1.0, and 10 μg/kg BW) alone did not induce acid output. Furthermore, in comparison with the vehicle administration, the co-administration of low-dose (1 μg/kg BW) motilin and ghrelin significantly stimulated gastric acid secretion, whereas either motilin (1 μg/kg BW) or ghrelin (1 μg/kg BW) alone did not significantly induce gastric acid secretion. This indicates an additive role of ghrelin in motilin-induced gastric acid secretion. We then investigated the pathways of motilin/motilin and ghrelin-stimulated acid secretion using receptor antagonists. Treatment with YM 022 (a CCK-B receptor antagonist) and atropine (a muscarinic acetylcholine receptor antagonist) had no effect on motilin or motilin-ghrelin co-administration-induced acid output. In contrast, famotidine (a histamine H2 receptor antagonist) completely inhibited motilin-stimulated acid secretion and co-administration of motilin and ghrelin induced gastric acid output. This is the first report demonstrating that motilin stimulates gastric secretion in mammals. Our results also suggest that motilin and co-administration of motilin and ghrelin stimulate gastric acid secretion via the histamine-mediated pathway in suncus.
authors.affiliation: Area of Regulatory Biology, Division of Life Science, Graduate School of Science and Engineering, Saitama University, Saitama, Japan.
authors.forename: Chayon
authors.initials: C
authors.lastname: Goswami
authors.affiliation: Area of Regulatory Biology, Division of Life Science, Graduate School of Science and Engineering, Saitama University, Saitama, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Shimada
authors.affiliation: Area of Regulatory Biology, Division of Life Science, Graduate School of Science and Engineering, Saitama University, Saitama, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Yoshimura
authors.affiliation: Area of Regulatory Biology, Division of Life Science, Graduate School of Science and Engineering, Saitama University, Saitama, Japan.
authors.forename: Anupom
authors.initials: A
authors.lastname: Mondal
authors.affiliation: Laboratory of Animal Management and Resources, Department of Zoology, Okayama University of Science, Okayama, Japan.
authors.forename: Sen-ichi
authors.initials: S
authors.lastname: Oda
authors.affiliation: Faculty of Pharmaceutical Sciences, Josai University, Saitama, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Area of Regulatory Biology, Division of Life Science, Graduate School of Science and Engineering, Saitama University, Saitama, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Sakai
authors.affiliation: Area of Regulatory Biology, Division of Life Science, Graduate School of Science and Engineering, Saitama University, Saitama, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Sakata
mesh_terms: D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D015738:Famotidine / Q000494:pharmacology; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000502:physiology; D054439:Ghrelin / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D023421:Models, Animal; D009037:Motilin / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*; D012788:Shrews; D013270:Stomach / Q000187:drug effects / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000897:Anti-Ulcer Agents; D054439:Ghrelin; D009037:Motilin; D015738:Famotidine