The effect of CCKB/gastrin antagonists on stimulated gastric acid secretion in the anaesthetized rat.
1. The urethane-anaesthetized, vagotomised rat preparation was used to investigate the effects of the histamine H2-antagonist ranitidine, the proton pump inhibitor omeprazole and the CCKB/gastrin antagonists CI-988, PD 136450 and L-365,260 on pentagastrin-, histamine- and bethanechol-induced gastric acid secretion. 2. The novel CCKB/gastrin antagonists CI-988 and PD 136450, and L-365,260 dose-dependently inhibited pentagastrin-induced secretion. The ED50 value for PD 136450 was 0.05 mumol kg-1, the same following intravenous or subcutaneous administration. 3. CI-988 and PD 136450 administered subcutaneously at dose levels highly effective for antagonism of pentagastrin responses had no effect on basal acid secretion. 4. Ranitidine inhibited pentagastrin-, bethanechol-, and histamine-induced acid secretion, whereas the CCKB/gastrin antagonists inhibited only the secretory response to pentagastrin. 5. The selective CCKA antagonist, devazepide, was inactive at up to 300 mumol kg-1 i.p. against the three stimulants of acid secretion. 6. CI-988 and PD 136450 will be useful research tools with which to investigate the role of CCKB/gastrin receptors in gastric acid secretion and the trophic activities of gastrin and cholecystokinin (CCK) on the gastrointestinal tract.
Parke-Davis Neuroscience Research Centre, Addenbrookes Hospital Site, Cambridge.
N J
NJ
Hayward
M
M
Harding
S A
SA
Lloyd
A T
AT
McKnight
J
J
Hughes
G N
GN
Woodruff
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D001570:Benzodiazepinones / Q000494:pharmacology; D001626:Bethanechol Compounds / Q000494:pharmacology; D002766:Cholecystokinin / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D005744:Gastric Acid / Q000378:metabolism*; D005755:Gastrins / Q000037:antagonists & inhibitors*; D006632:Histamine / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008536:Meglumine / Q000031:analogs & derivatives / Q000494:pharmacology; D009853:Omeprazole / Q000494:pharmacology; D010671:Phenylurea Compounds; D011899:Ranitidine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors
D014151:Anti-Anxiety Agents; D001570:Benzodiazepinones; D001626:Bethanechol Compounds; D005755:Gastrins; D007211:Indoles; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin; C065599:PD 134308; C058121:L 365260; D008536:Meglumine; D001285:Atropine; D006632:Histamine; D011899:Ranitidine; D002766:Cholecystokinin; D009853:Omeprazole