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Am J Physiol Regul Integr Comp Physiol (October 31, 2002). doi:10.1152/ajpregu.00484.2002
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Articles in PresS, published online ahead of print October 31, 2002
Am J Physiol Regu Physiol, 10.1152/ajpregu.00484.2002
Submitted on August 14, 2002
Accepted on September 12, 2002

Effects of Peripheral CCK Receptor Blockade on Gastric Emptying in Rats

Roger D Reidelberger1*, Linda Kelsey2, Dean Heimann3, and Martin Hulce4

1 Veterans Administration Medical Center, Omaha, NE, USA; Department of Biomedical Sciences, Creighton University, School of Medicine, Omaha, NE, USA
2 Veterans Administration Medical Center, Omaha, NE, USA
3 Department of Biomedical Sciences, Creighton University, School of Medicine, Omaha, NE, USA
4 Department of Chemistry, Creighton University, School of Medicine, Omaha, NE, USA

* To whom correspondence should be addressed. E-mail: rogerr{at}creighton.edu.

Type A cholecystokinin receptor (CCKAR) antagonists differing in blood-brain barrier permeability [devazepide penetrates; the dicyclohexylammonium salt of N{alpha}-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 3000 nmol kg-1 h-1 IV) or devazepide (2.5 µmol kg-1 IV) and either a 15 min IV 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. IV 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.




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