title: Histamine mediates the stimulatory action of ghrelin on acid secretion in rat stomach.
abstract: Ghrelin, a novel growth hormone-releasing peptide, is present in the rat and human stomach and is known to stimulate acid secretion and stomach motility. However, the mechanism of action of ghrelin is not fully understood. In the present study, we attempted to elucidate the role of histamine in ghrelin-induced acid secretion in rat stomach. Intravenous administration of ghrelin at 0.8 to 20 microg/kg dose dependently increased gastric acid secretion, as measured by the gastric lumen perfusion method. The maximum response was almost equal to that of gastrin (20 microg/kg). These actions were abolished by bilateral subdiaphragmatic vagotomy. Famotidine (0.33 mg/kg) also completely inhibited the effects of ghrelin. Furthermore, ghrelin increased histidine decarboxylase (HDC) messenger RNA (mRNA) levels, as measured by real-time reverse transcription-polymerase chain reaction using LightCycler. The action of ghrelin on HDC mRNA was abolished by vagotomy. Ghrelin did not affect histamine release from isolated vascularly perfused rat stomach. Taken together, these results suggest that ghrelin stimulates gastric acid secretion via a mechanism involving activation of vagal efferent nerve and histamine release from gastric enterochromaffin-like cells.
authors.affiliation: Department of Internal Medicine, Saitama Medical Center, Saitama Medical School, 1821 Kamoda Tsujido-machi, Kawagoe-City, Saitama 350-8550, Japan. kjyakabi@saitama-med.ac.jp
authors.forename: Koji
authors.initials: K
authors.lastname: Yakabi
authors.forename: Shoki
authors.initials: S
authors.lastname: Ro
authors.forename: Tsuneko
authors.initials: T
authors.lastname: Onouhi
authors.forename: Teruyuki
authors.initials: T
authors.lastname: Tanaka
authors.forename: Shino
authors.initials: S
authors.lastname: Ohno
authors.forename: Seiichi
authors.initials: S
authors.lastname: Miura
authors.forename: Yukimi
authors.initials: Y
authors.lastname: Johno
authors.forename: Kiyoshige
authors.initials: K
authors.lastname: Takayama
mesh_terms: D000818:Animals; D015738:Famotidine / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism*; D054439:Ghrelin; D013006:Growth Hormone; D006632:Histamine / Q000378:metabolism*; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D006640:Histidine Decarboxylase / Q000235:genetics; D008297:Male; D036361:Peptide Hormones / Q000494:pharmacology*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013270:Stomach / Q000187:drug effects / Q000294:innervation; D014628:Vagotomy
chemical_list: D054439:Ghrelin; D006635:Histamine H2 Antagonists; D036361:Peptide Hormones; D012333:RNA, Messenger; D015738:Famotidine; D006632:Histamine; D013006:Growth Hormone; D006640:Histidine Decarboxylase