10 - Selective Cholecystokinin A and Cholecystokinin B/Gastrin Receptor Agonists

Abstract

Publisher Summary Cholecystokinin (CCK) is a brain–gut peptide that displays a wide range of biological activities in the brain and periphery. Two subtypes of CCK receptors, A and B, have been identified in the brain and periphery. The CCK-A (alimentary) type exists in the vagus, stomach, pancreas, gallbladder, intestinal smooth muscle, and specific brain nuclei. The CCK-B (brain) receptor has been identified in areas of the central nervous system (CNS). The classification of the two subtypes was based on the affinity of CCK peptide fragments for receptors in the cortex and pancreas. CCK-B receptors are less discriminating than the CCK-A receptors and possess high affinity for CCK-8, CCK-8(DS), CCK-4, and gastrin. The CCK-B receptor and the gastrin receptor on the gastric mucosa have similar pharmacological profiles, and these two receptors can be conveniently referred to as the CCK-B/gastrin type. CCK receptors couple to guanine nucleotide-binding proteins and may have seven transmembrane domains. The CCK-A receptors enhance phosphoinositide (PI) hydrolysis and intracellular calcium levels. This chapter describes many specific agonists and antagonists of both subtypes of CCK receptors. It also describes the in vitro assays used in the laboratory to develop and characterize the selective CCK-A and CCK-B/ gastrin receptor agonists.