Evolution of the Cholecystokinin and Gastrin Peptides and Receptors1

SYNOPSIS. The intestinal hormone, cholecystokinin (CCK), and the stomach hormone, gastrin, form a simple two member family of peptides with much to offer students of hormone and receptor evolution. They share a common carboxyl-terminal tetrapeptide sequence, which is the bioactive site of each peptide and is also antigenic, making heterologous biological and immunological assays feasible. Current evidence indicates that CCK evolved in chordate ancestors and that gastrinlike peptides that separately regulate stomach functions evolved from an ancestral CCK at the level of the divergence of tetrapods from fish. This tentative conclusion may require modification when the two separate CCKand gastrin-like peptides recently identified in the dogfish shark are characterized further. The CCK-X receptor appears to be ancestral to the CCK-A and CCK-B receptors identified in amniotes. The evolution of gastrin and of CCK-A and -B receptors may have played roles in the evolution of the stomach and the evolution of endothermy in vertebrate phylogeny.