Effects of peripheral CCK receptor blockade on gastric emptying in rats

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology integrative and comparative physiology, 2003-01, Vol.284 (1), p.66-R75
• Main Authors: Reidelberger, Roger D, Kelsey, Linda, Heimann, Dean, Hulce, Martin
• Format: Article
• Language: English
• Subjects: Animals; Antibodies - immunology; Antibodies - pharmacology; Caseins - administration & dosage; Caseins - pharmacology; Cholecystokinin - antagonists & inhibitors; Cholecystokinin - immunology; Cholecystokinin - metabolism; Cholecystokinin - pharmacology; Devazepide - pharmacology; Drug Administration Routes; Fat Emulsions, Intravenous - administration & dosage; Fat Emulsions, Intravenous - pharmacology; Gastric Emptying - drug effects; Hormone Antagonists - pharmacology; Male; Maltose - administration & dosage; Maltose - pharmacology; Peptide Fragments - antagonists & inhibitors; Peptide Fragments - immunology; Peptide Fragments - metabolism; Peptide Fragments - pharmacology; Peptones - administration & dosage; Peptones - pharmacology; Quinolines - pharmacology; Rats; Rats, Sprague-Dawley; Receptors, Cholecystokinin - antagonists & inhibitors; Receptors, Cholecystokinin - metabolism
• ISSN: 0363-6119; 1522-1490
• DOI: 10.1152/ajpregu.00484.2002

1  Veterans Affairs Medical Center, Omaha 68105, and 2  Departments of Biomedical Sciences and 3  Chemistry, Creighton University, School of Medicine, Omaha, Nebraska 68178 Type A CCK receptor (CCKAR) antagonists differing in blood-brain barrier permeability [devazepide penetrates; the dicyclohexylammonium salt of N -3-quinolinoyl- D -Glu- N,N -dipentylamide (A-70104) does not] were used to test the hypothesis that duodenal nutrient-induced inhibition of gastric emptying is mediated by CCKARs located peripheral to the blood-brain barrier. Rats received A-70104 (700 or 3,000   nmol · kg 1 · h 1 iv) or devazepide (2.5 µmol/kg iv) and either a 15-min intravenous infusion of CCK-8 (3 nmol · kg 1 · h 1 ) or duodenal infusion of casein, peptone, Intralipid, or maltose. Gastric emptying of saline was measured during the last 5 min of each infusion. A-70104 and devazepide abolished the gastric emptying response to a maximal inhibitory dose of CCK-8. Each of the macronutrients inhibited gastric emptying. A-70104 and devazepide attenuated inhibitory responses to each macronutrient. Intravenous injection of a CCK antibody to immunoneutralize circulating CCK had no effect on peptone or Intralipid-induced responses. Thus endogenous CCK appears to act in part by a paracrine or neurocrine mechanism at CCKARs peripheral to the blood-brain barrier to inhibit gastric emptying. receptor antagonist; devazepide; A-70104; immunoneutralization; macronutrient