Abdominal vagal mediation of the satiety effects of CCK in rats

Abstract

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.

Appetite control

“…The vagal nerve projects to the NTS, which in turn relays information to the hypothalamus (Schwartz et al 2000). Peripheral CCK may act both on the vagal nerve and directly on the CNS by crossing the blood-brain barrier (Reidelberger et al 2003). Evidence from the CCK A receptor-knockout (OLETF) rat suggests that CCK may act on the DMH to suppress NPY levels Bi et al 2001).…”

Proopiomelanocortin Neurons in Nucleus Tractus Solitarius Are Activated by Visceral Afferents: Regulation by Cholecystokinin and Opioids

“…However, CCK1 receptor antagonists that cross the blood-brain barrier stimulate food intake in vagotomized animals (Reidelberger et al, 2004). Such observations, along with considerable evidence of CNS CCK1 receptor expression, raise the possibility that CCK has both central and peripheral actions (Ritter, 2004).…”

Extracellular Signal-Regulated Kinase 1/2 Signaling Pathway in Solitary Nucleus Mediates Cholecystokinin-Induced Suppression of Food Intake in Rats

“…Therefore, we can assume that the peripherally administered CCK acts at least partly through this vagal afferent, glutamatergic pathway in our experiments. However, previous experiments using direct brain injections of CCK (Schick et al, 1986) and recent evidence gathered with CCK-A receptor antagonists that do or do not penetrate the blood-brain barrier (Reidelberger et al, 2004) suggest that, in addition to mediation by vagal afferents, exogenous CCK and endogenous CCK from the gut can affect food intake by direct action in the brain.…”