GASTRIN AND CHOLECYSTOKININ OF THE BULLFROG, RANA-CATESBEIANA, HAVE DISTINCT EFFECTS ON GALLBLADDER MOTILITY AND GASTRIC-ACID SECRETION IN-VITRO

Many regulatory peptides form families with at least two homologous me mbers. For several such families the divergence of the individual memb ers from a common ancestor can be dated to early in vertebrate history . Cholecystokinin (CCK) and gastrin were originally identified in mamm als. Recently, two distinct members of the CCK/gastrin family were ide ntified in the bullfrog (Rana catesbeiana), termed CCK and gastrin. Fr og gastrin is very similar to CCK in the region defining biological ac tivity. To evaluate whether the two endogenous peptides have distinct properties, their effects were studied in typical target organs. While porcine gallbladder responded equally to frog gastrin-8 and CCK-8, EC 50 values for stimulation of bullfrog gallbladder contractions were 49 0 nM (gastrin) and 69 nM (CCK). In contrast, gastrin appeared to be a more potent stimulant of acid secretion than CCK; the estimated EC50 v alues are 3.1 and 17.2 nM, respectively. Furthermore, gastrin had a si gnificantly higher efficacy than CCK-8s. Thus, in spite of their close structural resemblance, there are clear differences between the two e ndogenous peptides in their action on gallbladder and gastric mucosa. It is concluded that there are distinct gastrin and CCK functions alre ady at the amphibian level of evolution. (C) 1998 Academic Press.