Cholecystokinin and the gut-brain axis

Cholecystokinin (CCK) is a gastrointestinal (GI) hormone that has many effects, including, but not limited to, inhibition of food intake (Gibbs et al., 1973), inhibition of gastric emptying (Debas et al., 1975; Moran & McHugh, 1982; Conover et al., 1988; Schwartz et al., 1991; Moran et al., 1993), stimulation of gall bladder contractions (Torsoli et al., 1961), stimulation of pancreatic amylase, lipase, tyrosine, and chymotrypsin secretion (Beglinger et al., 1985; Fink et al., 1985; Reidelberger & Solomon, 1986; Einarsson et al., 1997), inhibition of gastrin-induced acid secretion (Lloyd et al., 1992), relaxation of the sphincter of Oddi and duodenum (Torsoli et al., 1961; Grider, 1994), and decreasing gastric pressure (Raybould et al., 1987; Melton et al., 1992). All these effects are aimed at maximizing digestion and nutrient uptake. The majority of CCK-mediated intestinal feedback is mediated via the activation of extrinsic neural pathways, specifically the vagal afferent pathway. This chapter will discuss the processes and mechanisms involved, from activation of CCK1 receptors on vagal afferent nerve terminals, transmission of the signals along the pathway, including intracellular transduction mechanisms, modulation of expression of other receptors for regulatory peptides, signaling within the brain stem and higher centers, through to functional consequences.