AJP - Gastrointestinal and Liver Physiology, Vol 248, Issue 1 98-102, Copyright © 1985 by American Physiological Society
N-terminal fragments of CCK-(26-33) as cholecystokinin receptor antagonists in guinea pig pancreatic acini
J. D. Gardner, M. Knight, V. E. Sutliff and R. T. Jensen
In the present study we synthesized different N-terminal fragments and
analogues of the C-terminal octapeptide of cholecystokinin [CCK-(26-33)]
and examined their actions on dispersed acini prepared from guinea pig
pancreas. None of the N-terminal fragments or analogues altered basal
amylase release. Analogues of CCK-(26-32), CCK-(26-31), and CCK-(26-30)
inhibited CCK-(26-33)-stimulated amylase, and there was a close correlation
between the ability of an analogue to inhibit stimulated amylase and the
analogue's ability to inhibit binding of 125I-cholecystokinin.
N-acetyl-CCK-(26-29)-amide at concentrations as high as 100 microM did not
inhibit CCK-(26-33)-stimulated amylase release or binding of 125I-CCK. For
those analogues that antagonized CCK-(26-33)-stimulated amylase release the
antagonism was of the competitive type and was specific for those
secretagogues that interact with the cholecystokinin receptor. Removing the
C-terminal amide from N-acetyl-CCK-(26-31)-amide caused a 10-fold decrease
in the inhibitory potency, whereas removing the C-terminal amide from
N-acetyl-CCK-(26-30)-amide did not alter the inhibitory potency of the
peptide. Removing the sulfate ester from the tyrosine residue in position
27 of N-acetyl-CCK-(26-31) did not alter the inhibitory potency of the
peptide, whereas removing the sulfate ester from the tyrosine residue in
position 27 of N-acetyl-(26-30) caused a three- to fivefold decrease in the
inhibitory potency of the peptide.(ABSTRACT TRUNCATED AT 250 WORDS)
