Abdominal vagal mediation of the satiety effects of CCK in rats.
CCK type 1 (CCK1) receptor antagonists differing in blood-brain barrier permeability were used to test the hypothesis that satiety is mediated in part by CCK action at CCK1 receptors on vagal sensory nerves innervating the small intestine. Devazepide penetrates the blood-brain barrier; A-70104, the dicyclohexylammonium salt of N alpha-3-quinolinoyl-D-Glu-N,N-dipentylamide, does not. At dark onset, non-food-deprived control rats and rats with subdiaphragmatic vagotomies received a bolus injection of devazepide (2.5 micromol/kg i.v.) or a 3-h infusion of A-70104 (3 micromol.kg(-1).h(-1) i.v.) either alone or coadministered with a 2-h intragastric infusion of peptone (0.75 or 1 g/h). Food intake was determined from continuous computer recordings of changes in food bowl weight. In control rats both antagonists stimulated food intake and attenuated the anorexic response to intragastric infusion of peptone. In contrast, only devazepide was effective in stimulating food intake in vagotomized rats. Thus endogenous CCK appears to act both at CCK1 receptors beyond the blood-brain barrier and by a CCK1 receptor-mediated mechanism involving abdominal vagal nerves to inhibit food intake.
Reidelberger
Roger D
RD
Department of Veterans Affairs-Nebraska Western Iowa Health Care System, and Department of Biomedical Sciences, Creighton University, Omaha, Nebraska, USA. Roger.Reidelberger@med.va.gov
Hernandez
Jessica
J
Fritzsch
Bernd
B
Hulce
Martin
M
D000005:Abdomen / Q000294:innervation; D000818:Animals; D002766:Cholecystokinin / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D020109:Devazepide / Q000008:administration & dosage / Q000494:pharmacology; D004435:Eating / Q000187:drug effects / Q000502:physiology; D006727:Hormone Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D007262:Infusions, Intravenous; D008297:Male; D010461:Peptones / Q000008:administration & dosage / Q000494:pharmacology; D011804:Quinolines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors / Q000502:physiology; D012528:Satiety Response / Q000502:physiology*; D012844:Sincalide / Q000008:administration & dosage / Q000494:pharmacology; D014628:Vagotomy; D014630:Vagus Nerve / Q000502:physiology*
D006727:Hormone Antagonists; D010461:Peptones; D011804:Quinolines; D011949:Receptors, Cholecystokinin; C063047:A 65186; D002766:Cholecystokinin; D020109:Devazepide; D012844:Sincalide