Camostate- and caerulein-induced delay of gastric emptying in the rat: effect of CCK receptor antagonists.
The effect of camostate, a potent releaser of endogenous cholecystokinin (CCK), and of caerulein, an amphibian peptide mimicking the biological actions of CCK, as well as of selective CCK receptor antagonists on gastric emptying of liquids was studied in the rat. Oral administration of camostate (200 mg/kg with the liquid test meal preceded by the same dose 10 min before the meal) significantly delayed gastric emptying of saline, an effect which was completely blocked by previous administration of the CCKA receptor antagonist, devazepide, at a dose (1 mg/kg i.v.) unable to modify the emptying rate when administered alone. Caerulein (0.03-30 nmol/kg i.v.) also delayed the emptying rate in a dose-dependent manner, with an ID50 of 3.94 nmol/kg. The effect of the peptide was also inhibited by devazepide. The CCKB receptor antagonist, L365,260 (3R-(+)-N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1, 4-benzodiazepine-3-yl)-N'-(3-methylphenyl)-urea; 3 mg/kg i.v.), was completely unable to modify the CCK (both endogenous and exogenous)-induced delay in gastric emptying. Repeated (7 days) camostate administration did not modify the gastric motor response to endogenous CCK, thus, suggesting that adaptation did not take place. These results demonstrate that endogenous and exogenous CCK delays gastric emptying of liquids through stimulation of CCKA receptors and suggest that adaptation of the gastric motor response to CCK does not occur.
Varga
G
G
Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary.
Scarpignato
C
C
D000704:Analysis of Variance; D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D002108:Ceruletide / Q000494:pharmacology*; D020109:Devazepide; D004305:Dose-Response Relationship, Drug; D004952:Esters; D016670:Gabexate / Q000031:analogs & derivatives*; D005746:Gastric Emptying / Q000187:drug effects* / Q000502:physiology; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D006146:Guanidines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006727:Hormone Antagonists / Q000494:pharmacology; D008297:Male; D010671:Phenylurea Compounds; D011480:Protease Inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors*
D001570:Benzodiazepinones; D004952:Esters; D005765:Gastrointestinal Agents; D006146:Guanidines; D006727:Hormone Antagonists; D010671:Phenylurea Compounds; D011480:Protease Inhibitors; D011949:Receptors, Cholecystokinin; C034532:camostat; C058121:L 365260; D016670:Gabexate; D002108:Ceruletide; D020109:Devazepide