Identification of cholecystokinin/gastrin peptides in frog and turtle. Evidence that cholecystokinin is phylogenetically older than gastrin.

Peptides homologous to mammalian cholecystokinin (CCK) and gastrin in brain, antrum, and small intestine of an amphibian (the bullfrog, Rana catesbeiana) and a reptile (the turtle, Pseudomys scripta) were characterized. All tissues contained peptides reacting with antisera specific for the carboxyamidated C-terminal tetrapeptide common for CCK and gastrin. Extracts of all tissues, except the turtle antrum, also reacted with an antiserum specific for mammalian sulfated CCK, while no extract contained peptides reacting with an antiserum specific for mammalian gastrin. Both species contained predominantly small acidic forms in the brain and larger less acidic forms in the antrum and intestine. The antral peptides of both species were identified. The largest frog gastrin was a 47-residue peptide: DLLASLTHEQ KQLIMSQLLP ELLSELSNAE DHLHPMRDRD YAGWMDF.NH2. The largest turtle gastrin was a 52-residue peptide: DLLEALSQDQ KLLMAKFLPH IYAELANREG NWHEDAALRP LHDHDYPGWM DF.NH2. They display 51% similarity. Having Tyr in position 7 from the C-terminus, both resemble structurally mammalian CCK rather than gastrin, which suggests that CCK is phylogenetically older than gastrin. The turtle antral peptide contains a Tyr followed by Pro as in chicken gastrin. Thus, apparently at the stage of reptiles, a route different from the mammalian was taken in order to evolve a specific gastrin function.