AJP - Gastrointestinal and Liver Physiology, Vol 250, Issue 4 405-G411, Copyright © 1986 by American Physiological Society
Action of cholecystokinin analogues on exocrine and endocrine rat pancreas
M. Otsuki, Y. Okabayashi, A. Ohki, T. Oka, M. Fujii, T. Nakamura, N. Sugiura, N. Yanaihara and S. Baba
In the present study we have examined the abilities of
cholecystokinin-(26-33)-amide [CCK-(26-33)-NH2, CCK-8], nonsulfated
CCK-(26-33)-NH2 (desulfated CCK-8), CCK-(30-33)-NH2 (CCK-4), CCK-(26-33)-OH
(deamidated CCK-8), and succinyl CCK-(27-31)-NH2 (Suc-Des-Asp6,Phe7-CCK-7)
to stimulate exocrine pancreatic secretion from both isolated pancreatic
acini and isolated perfused pancreas. We have also compared this action
with their ability to cause insulin release. The modification of either the
N- or C-terminal amino acid residues of CCK-8 decreased in potency, but the
magnitude of the stimulation of enzyme secretion caused by a maximally
effective peptide concentration was the same. The minimal effective
concentration of CCK-8, desulfated CCK-8, and CCK-4 for insulin release
from the isolated rat pancreas in the presence of 8.3 mM glucose was the
same as that for pancreatic exocrine secretion. In contrast, the
concentrations of deamidated CCK-8 and Suc-Des-Asp6,Phe7-CCK-7 required to
produce insulin release were 5-10 times higher than those required to cause
stimulation of pancreatic enzyme and juice secretion. It is concluded
therefore that the N-terminal 4-amino acid residues or the C-terminal
2-amino acid residues of CCK-8 are not essential for biological activity
but do contribute to its potency. In addition, the C-terminal 2-amino acid
residues and an amide group in the C-terminal phenylalanine residue of
CCK-8 appear to be important determinants of the insulin-releasing activity
of the CCK peptides.
