N-acetyl-GRP(20-26)-O-CH3 reverses intracisternal bombesin-induced inhibition of gastric acid secretion in rats.
Intracisternal injection of 19 pmoles of bombesin in light-ether-anesthetized rats, five minutes after intracisternal vehicle, produced a 75% and 63% inhibition in gastric acid output and concentration, respectively, in 2-hour pylorus-ligated rats. Pretreatment of rats with the characterized peripheral bombesin antagonist N-acetyl-GRP(20-26)-O-CH3 (1 nmole) reversed the inhibitory effect of bombesin on gastric acid output and concentration. In contrast, the related bombesin antagonist N-acetyl-GRP-O-CH2-CH3 (1 nmole) was ineffective in this system. In urethane-anesthetized, acute gastric fistula rats infused with pentagastrin, intracisternal N-acetyl-GRP(20-26)-O-CH3 protected against the inhibition in gastric acid output produced by intracisternal bombesin (19 pmoles). Thus the recently characterized peripheral bombesin antagonist N-acetyl-GRP(20-26)-O-CH3 also appears to be effective in antagonizing central bombesin-induced inhibition in gastric acid secretion in two models. This represents a first report of a synthetic bombesin antagonist effective in reversing central bombesin-induced effects on gastric function.
Stephens
R L
RL
Department of Physiology, Ohio State University, Columbus 43210.
Horner
P
P
Drapeau
G
G
D000818:Animals; D001839:Bombesin / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D005744:Gastric Acid / Q000378:metabolism*; D005747:Gastric Fistula; D008026:Ligation; D009842:Oligopeptides; D010418:Pentagastrin / Q000008:administration & dosage; D010455:Peptides / Q000494:pharmacology; D011708:Pylorus; D051381:Rats; D011919:Rats, Inbred Strains
C071104:GRP, N-acetyl (20-26) methyl ester-; D009842:Oligopeptides; D010455:Peptides; C071106:N-acetyl-gastrin releasing peptide ethyl ester; D010418:Pentagastrin; D001839:Bombesin