AJP - Gastrointestinal and Liver Physiology, Vol 242, Issue 2 161-G167, Copyright © 1982 by American Physiological Society
Cyclic nucleotide antagonists of cholecystokinin: structural requirements for interaction with the cholecystokinin receptor
N. Barlas, R. T. Jensen, M. C. Beinfeld and J. D. Gardner
Previously, we have found that, in pancreatic acini, butyryl derivatives of
cGMP antagonize the action of cholecystokinin by inhibiting binding of the
peptide to its membrane receptors. In the present study, we found that
derivatives of cAMP and cIMP can also inhibit binding of cholecystokinin as
well as its actions on acinar cell function. Moreover, the inhibition
caused by cyclic nucleotide derivatives did not require the presence of a
butyryl moiety, because certain 8-bromo-cyclic nucleotides also inhibited
the interaction of cholecystokinin with its receptors. Cyclic nucleotide
derivatives can also increase pancreatic enzyme secretion; however, for the
various cyclic nucleotides tested, there was no apparent correlation
between their abilities to stimulate enzyme secretion and their abilities
to antagonize the actions of cholecystokinin. Finally, cyclic nucleotide
derivatives also inhibited binding of 125I-cholecystokinin to antibodies
that were specific for the biologically active, C-terminal region of
cholecystokinin. Thus, certain cyclic nucleotide derivatives possess a
conformational structural which resembles that of the biologically active
portion of cholecystokinin, and this structural similarity accounts for the
abilities of these nucleotide derivatives to interact with cholecystokinin
receptors and, by so doing, to inhibit the action of cholecystokinin on its
target tissues.
