Comparison of the actions of acylated and desacylated ghrelin on acid secretion in the rat stomach.
BACKGROUND
Ghrelin, a growth-hormone-releasing peptide, has two major molecular forms: acylated (acyl) and desacylated (desacyl). Recent studies suggest different roles for these two forms. In the present study, we compared desacyl and acyl ghrelin with regard to acid secretion and histamine production in the rat stomach.


METHODS
We performed in vivo experiments using gastric lumen-perfused rats. The effects of the two forms of ghrelin on gastrin (gastrin-17)-stimulated acid secretion were also examined. Furthermore, to examine the effects of ghrelin on histamine production, histidine decarboxylase messenger ribonucleic acid in the gastric corpus mucosa was measured by reverse transcription-polymerase chain reaction.


RESULTS
Intravenous administration of acyl ghrelin at 20 μg/kg increased gastric acid secretion to 4.8 times greater than control levels. However, desacyl ghrelin had no effect on acid secretion, even at 200 μg/kg. Acyl ghrelin enhanced gastrin-stimulated acid secretion while desacyl ghrelin did not. Vagotomy markedly inhibited the enhancement of gastrin-stimulated acid secretion by acyl ghrelin. Acyl ghrelin increased histidine decarboxylase messenger ribonucleic acid concentration by 2.3 times compared with basal levels at 1 h after administration and by 2.7 times at 2 h after administration; desacyl ghrelin had no such effect. Synergism between acyl ghrelin and gastrin was seen regarding histidine decarboxylase messenger ribonucleic acid concentration.


CONCLUSIONS
The results indicate that acyl ghrelin stimulates gastric acid secretion via a mechanism involving activation of the vagus nerve and histamine release and synthesis and that desacyl ghrelin has no action on gastric acid secretion. Furthermore, the results demonstrate synergism between gastrin and acyl ghrelin in terms of gastric acid secretion via a mechanism involving histamine release and synthesis.
Sakurada
Tomoya
T
Department of Gastroenterology and Hepatology, Saitama Medical Center, Saitama Medical University, Kawagoe, Saitama, Japan. sakurada@saitama-med.ac.jp
Ro
Shoki
S
Onouchi
Tsuneko
T
Ohno
Shino
S
Aoyama
Tohru
T
Chinen
Katsuya
K
Takabayashi
Hidehiko
H
Kato
Shingo
S
Takayama
Kiyoshige
K
Yakabi
Koji
K
D000215:Acylation; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism; D005755:Gastrins / Q000008:administration & dosage; D054439:Ghrelin / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D006632:Histamine / Q000096:biosynthesis* / Q000378:metabolism; D006640:Histidine Decarboxylase / Q000378:metabolism; D006801:Humans; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013270:Stomach / Q000187:drug effects*; D013997:Time Factors; D014630:Vagus Nerve / Q000378:metabolism
D005755:Gastrins; D054439:Ghrelin; D012333:RNA, Messenger; C422650:ghrelin, des-n-octanoyl; D006632:Histamine; D006640:Histidine Decarboxylase