Effects of peripheral CCK receptor blockade on gastric emptying in rats.
Type A CCK receptor (CCKAR) antagonists differing in blood-brain barrier permeability [devazepide penetrates; the dicyclohexylammonium salt of Nalpha-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 micromol/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.
Reidelberger
Roger D
RD
Veterans Affairs Medical Center, Omaha 68105, USA.
Kelsey
Linda
L
Heimann
Dean
D
Hulce
Martin
M
D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D002364:Caseins / Q000008:administration & dosage / Q000494:pharmacology; D002766:Cholecystokinin / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D020109:Devazepide / Q000494:pharmacology; D004333:Drug Administration Routes; D005217:Fat Emulsions, Intravenous / Q000008:administration & dosage / Q000494:pharmacology; D005746:Gastric Emptying / Q000187:drug effects*; D006727:Hormone Antagonists / Q000494:pharmacology; D008297:Male; D008320:Maltose / Q000008:administration & dosage / Q000494:pharmacology; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D010461:Peptones / Q000008:administration & dosage / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000906:Antibodies; D002364:Caseins; D005217:Fat Emulsions, Intravenous; D006727:Hormone Antagonists; D010446:Peptide Fragments; D010461:Peptones; D011804:Quinolines; D011949:Receptors, Cholecystokinin; C410885:cholecystokinin 8; C063047:A 65186; D008320:Maltose; D002766:Cholecystokinin; D020109:Devazepide