Evidence that endogenous GRP in rat stomach mediates omeprazole-induced hypergastrinemia.
To investigate the physiological role of endogenous gastrin-releasing peptide (GRP) in regulating the release of gastrin, we evaluated the response of intragastric pH, gastrin, and GRP after omeprazole treatment in rats. A significant elevation of the plasma level of GRP (P < 0.01) and a significant reduction of the antral content of GRP (P < 0.05) were observed after the administration of 100 mg/kg omeprazole. The antral content of GRP was significantly decreased 12 h after omeprazole administration and thereafter gradually returned to control levels. Peak values for intragastric pH and plasma GRP were observed 3 h after omeprazole administration and before the peak of serum gastrin. The bombesin antagonist [D-Phe6]-bombesin-(6,13)-methyl ester significantly inhibited gastrin release after omeprazole treatment (P < 0.05). These observations indicate that omeprazole-induced inhibition of acid secretion stimulates the release of GRP and suggest that the secretion of GRP induced by omeprazole may stimulate the secretion of gastrin, at least in the early phase.
Takehara
Y
Y
First Department of Internal Medicine, Hiroshima University School of Medicine, Japan.
Sumii
K
K
Tari
A
A
Yoshihara
M
M
Sumii
M
M
Haruma
K
K
Kajiyama
G
G
Wu
S V
SV
Walsh
J H
JH
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D005748:Gastric Fundus; D005753:Gastric Mucosa / Q000187:drug effects / Q000502:physiology*; D019886:Gastrin-Releasing Peptide; D005755:Gastrins / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism*; D005768:Gastrointestinal Hormones / Q000502:physiology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D009853:Omeprazole / Q000494:pharmacology*; D010455:Peptides / Q000097:blood / Q000494:pharmacology / Q000502:physiology*; D011706:Pyloric Antrum; D012333:RNA, Messenger / Q000096:biosynthesis; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014158:Transcription, Genetic
D000897:Anti-Ulcer Agents; D005755:Gastrins; D005768:Gastrointestinal Hormones; D010455:Peptides; D012333:RNA, Messenger; D019886:Gastrin-Releasing Peptide; D009853:Omeprazole