Cholecystokinin and its receptors in vertebrates and invertebrates

Recent studies have indicated that cholecystokinin (CCK) peptides have a long evolutionary history. However, whereas all vertebrates examined have been shown to contain CCK-like peptides, this has not been possible to demonstrate for all invertebrate groups. Immunostaining studies indicate that CCK peptides originate only in neurons in groups below the level of the protochordates. It seems likely that CCK gastrointestinal endocrine cells evolved first at the level of the protochordates, possibly from sensory gut neurons similar to those seen in the invertebrates. Immunochemical and biological studies of a few invertebrate CCK-like peptides suggest that those molecules are substantially different in structure from vertebrate CCKs. Gastrin appears to have evolved from CCK at the level of the appearance of amniotes in vertebrate phylogeny. In mammals, central and peripheral CCK receptors differ in specificity for CCK- and gastrin-like peptides. Comparative studies reveal that this is true for birds as well, but reptiles, amphibia, and fish brain and pancreas CCK receptors exhibit nearly identical specificity patterns. This suggests that the lower vertebrate CCK receptor is ancestral to the distinct brain and pancreas CCK receptors seen in birds and mammals.