Histamine mediates the stimulatory action of ghrelin on acid secretion in rat stomach.
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.
Yakabi
Koji
K
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
Ro
Shoki
S
Onouhi
Tsuneko
T
Tanaka
Teruyuki
T
Ohno
Shino
S
Miura
Seiichi
S
Johno
Yukimi
Y
Takayama
Kiyoshige
K
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
D054439:Ghrelin; D006635:Histamine H2 Antagonists; D036361:Peptide Hormones; D012333:RNA, Messenger; D015738:Famotidine; D006632:Histamine; D013006:Growth Hormone; D006640:Histidine Decarboxylase