AJP - Gastrointestinal and Liver Physiology, Vol 260, Issue 6 976-G982, Copyright © 1991 by American Physiological Society
Cionin, a protochordean hybrid of cholecystokinin and gastrin: biological activity in mammalian systems
B. Schjoldager, J. Park, A. H. Johnsen, T. Yamada and J. F. Rehfeld
Department of Medical Physiology, Rigshospitalet, University of Copenhagen, Denmark.
The protochordean octapeptide cionin is structurally a hybrid of mammalian
cholecystokinin (CCK) and gastrin, and thus their possible common ancestor.
To determine whether cionin behaves like CCK or gastrin, we examined its
effect on canine fundic somatostatin cells and on porcine and bovine
gallbladder muscles. Cionin released somatostatin with a potency (ED50 0.15
nM) and efficacy (14.8% of cell content) similar to that of CCK-8 (ED50
0.12 nM, efficacy 16.7%). The efficacies but not the potencies of CCK-8 and
cionin differed from those of sulfated gastrin (0.12 nM, 9.7%), nonsulfated
gastrin (0.20 nM, 9.4%), and nonsulfated CCK-8 (0.30 nM, 10.4%). CCK and
gastrin stimulated contractions of porcine gallbladder muscle strips in a
concentration-dependent manner with no differences in efficacy but with
characteristic differences in potency. CCK-8 and cionin displayed similar
potencies of ED50 2.0 and 2.6 nM; both were significantly different from
the ED50 of 0.4 microM for sulfated gastrin and 2.3 microM for nonsulfated
gastrin. CCK radioligand binding to membrane-enriched preparations of
porcine and bovine gallbladder muscularis was specific and of high
affinity. The equilibrium data revealed that binding of CCK and gastrin
peptides best fit a single site. CCK-8 and cionin displayed similar
affinities [Kd 0.5 nM (porcine), 0.5 nM (bovine, CCK) vs. Kd 0.8 and 0.9 nM
(cionin), respectively]. These differed again significantly from Kd 0.6 and
1.5 microM (sulfated gastrin) and 0.7 and 0.2 microM (nonsulfated gastrin).
The results show that cionin behaves like CCK rather than gastrin in
mammals.
