Inhibition of gastrin- and histamine-stimulated gastric acid secretion by gastrin and cholecystokinin antagonists in the rat.
The gastric acid inhibitory activities of a peptide-like gastrin receptor antagonist, Boc-beta Ala-Trp-Leu-Asp-O(CH2)2-Ph-4-F (CH-486), a nonpeptide gastrin/CCK-B antagonist (L-365,260), and a CCK-A antagonist (L-364,718), were investigated in the gastric lumen-perfused anaesthetized rat. A single i.v. injection of CH-486, 100 mumol/kg, reduced acid secretion stimulated by pentagastrin, 15 micrograms kg/h, to unstimulated levels, with no recovery within 50 min. Histamine-, 0.1 mumol kg/min, and carbamylcholine-, 0.1 mg kg/h, stimulated acid secretion were also reduced to unstimulated levels by CH-486, 100 mumol/kg, although with these latter two stimulants the inhibition was transient. L-365,260 and L-364,718, 10 mumol/kg, significantly inhibited both pentagastrin- and histamine-stimulated acid secretion, the latter again transiently. We conclude that the non-selective nature of the gastric acid inhibitory activity of gastrin antagonists might allow novel approaches to control gastric acid secretion in peptic ulcer disease.
Department of Physiological Sciences, Medical School, University of Newcastle upon Tyne, UK.
B H
BH
Hirst
K J
KJ
Elliott
H
H
Ryder
M
M
Szelke
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology*; D002766:Cholecystokinin / Q000037:antagonists & inhibitors*; D020109:Devazepide; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects*; D005755:Gastrins / Q000037:antagonists & inhibitors*; D006633:Histamine Antagonists / Q000494:pharmacology*; D007275:Injections, Intravenous; D008297:Male; D009842:Oligopeptides / Q000138:chemical synthesis / Q000494:pharmacology*; D010418:Pentagastrin / Q000037:antagonists & inhibitors*; D010671:Phenylurea Compounds; D051381:Rats; D011919:Rats, Inbred Strains; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors*
D001570:Benzodiazepinones; D005755:Gastrins; D006633:Histamine Antagonists; D009842:Oligopeptides; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin; C058121:L 365260; D002766:Cholecystokinin; D010418:Pentagastrin; D020109:Devazepide