Evolution of the cholecystokinin and gastrin peptides and receptors

The intestinal hormone, cholecystokinin (CCK), and the stomach hormone, gas trin, form a simple two member family of peptides with much to offer studen ts 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 fea sible, Current evidence indicates that CCK evolved in chordate ancestors,rs and that gastrin-like peptides that separately regulate stomach functions evolved from an ancestral CCK at the level of the divergence of tetrapods f rom fish, This tentative conclusion may require modification when the two s eparate CCK- and gastrin-like peptides recently identified in the dogfish s hark 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 g astrin 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.