Action of the cholecystokinin antagonist L364,718 on gastric emptying in the rat.
Cholecystokinin (CCK) is a potent inhibitor of gastric emptying. We have examined the effects of a novel potent peripheral CCK receptor antagonist (L364,718) on the action of endogenous and exogenous CCK octapeptide (CCK-8) on gastric emptying in the rat. In conscious gastric fistula rats, the recovery of liquid test meals of 3.0 ml (containing phenol red as a dilution marker) was determined over periods up to 8 min. Compared with saline, gastric emptying of solutions of peptone (4.5%), 50 mM HCl, and hyperosmolal saline was significantly delayed. The emptying of saline was also delayed by intravenous infusion of CCK-8 (400 pmol.kg-1.h-1). The CCK antagonist L364,718 reversed the effect of peptone in a dose-dependent manner and inhibited the response to exogenous CCK, but the emptying of physiological saline, 50 mM HCl, or hyperosmolal saline remained unchanged. A protease inhibitor (FOY-305) that is thought to release endogenous CCK by inhibiting negative feedback control by luminal proteases also delayed emptying, and this response was inhibited by L364,718. We conclude that CCK has a physiological role in the mediation of the effect of proteins on gastric emptying in the rat.
Green
T
T
Physiological Laboratory, University of Liverpool, United Kingdom.
Dimaline
R
R
Peikin
S
S
Dockray
G J
GJ
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology*; D002766:Cholecystokinin / Q000037:antagonists & inhibitors*; D020109:Devazepide; D004952:Esters; D016670:Gabexate / Q000031:analogs & derivatives*; D005746:Gastric Emptying / Q000187:drug effects*; D006146:Guanidines / Q000494:pharmacology; D008297:Male; D010447:Peptide Hydrolases / Q000494:pharmacology; D010461:Peptones / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012844:Sincalide / Q000494:pharmacology
D001570:Benzodiazepinones; D004952:Esters; D006146:Guanidines; D010461:Peptones; C034532:camostat; D016670:Gabexate; D002766:Cholecystokinin; D010447:Peptide Hydrolases; D020109:Devazepide; D012844:Sincalide