Cholecystokinin and gut-brain signalling.
Enteroendocrine cells of the gastrointestinal tract act as a luminal surveillance system responding to either the presence or absence of food in the gut lumen. Collectively, their secretory products regulate the course of digestion and determine the delivery of nutrient to the gut by controlling food intake. Afferent neurons of the vagus nerve are an important target of gut hormones, particularly for control of food intake. The intestinal hormone cholecystokinin (CCK) stimulates vagal afferent neuron discharge and also controls the expression of both G-protein coupled receptors and peptide neurotransmitters in these neurons. When plasma CCK concentrations are low, for example in fasting, vagal afferent neurons express cannabinoid CB1 and melanin concentrating hormone (MCH)-1 receptors, both of which are associated with stimulation of food intake. Post-prandial release of CCK rapidly down-regulates the expression of both receptors but stimulates the expression of Y2 receptors in neurons projecting to the stomach. In fasting, there is also increased expression in these neurons of the appetite-stimulating neuropeptide transmitter MCH, and depressed expression of the satiety-peptide cocaine and amphetamine regulated transcript (CART). Secretion of CCK decreases expression of MCH and increases expression of CART. The neurochemical phenotype of vagal afferent neurons therefore encodes whether or not there has been nutrient ingestion over the previous period. At low plasma concentrations of CCK vagal afferent neurons exhibit increased capacity for appetite-stimulation, while post-prandial concentrations of CCK lead to enhanced capacity for satiety signalling. A gatekeeper function can therefore be attributed to CCK in that its presence or absence influences the capacity of vagal afferent neurons to respond to other neurohormonal signals.
Physiological Laboratory, School of Biomedical Sciences, University of Liverpool, Crown St, Liverpool L69 3BX, UK. g.j.dockray@liverpool.ac.uk
Graham J
GJ
Dockray
D000818:Animals; D002766:Cholecystokinin / Q000378:metabolism / Q000502:physiology*; D005746:Gastric Emptying / Q000502:physiology; D006801:Humans; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000378:metabolism / Q000502:physiology; D041742:Upper Gastrointestinal Tract / Q000378:metabolism / Q000502:physiology*; D014630:Vagus Nerve / Q000378:metabolism / Q000502:physiology*; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
D009419:Nerve Tissue Proteins; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; D002766:Cholecystokinin