The role of cholecystokinin receptors in the short-term control of food intake

Abstract

Cholecystokinin (CCK) is a hormone secreted by the I-cells of the upper small intestine in response to fat, protein, and some nonnutrients, for example, camostat, and a peptide/neurotransmitter secreted by neurons of the central and peripheral nervous systems. There are multiple molecular forms of CCK, for example, CCK-8, CCK-33, and CCK-58, with an active site located within the first eight amino acids of the carboxyl terminus and with a sulfate group on the seventh tyrosine residue. Physiologically, CCK increases pancreatic secretions and gallbladder and smooth muscle contractions as well as inhibits gastric emptying and food intake. CCK evokes these responses by activating two G protein-coupled receptors: CCK(1) and CCK(2). CCK(1) receptors are located mainly in the alimentary tract and contain two affinity states, high and low, whereas CCK(2) receptors are found mainly in the brain. Although a CCK-mediated reduction in cumulative food intake occurs by the activation of low-affinity CCK(1) receptors located on vagal afferents, the vagus, and the splanchnic nerves are necessary for the reduction of meal size (MS) and the prolongation of the inter-meal interval (IMI) by CCK. Finally, the reduction of food intake by CCK occurs by three possible modes of action: paracrine, endocrine, and neurocrine; thus far, the data favor a paracrine mode. In addition, the gut, which is the main source of peripheral CCK, contains the first neuronal component that senses the presence of food, the enteric nervous system. The enteric nervous system may have a role in the reduction of MS and the prolongation of the IMI by CCK.