AJP - Gastrointestinal and Liver Physiology, Vol 262, Issue 6 1113-G1120, Copyright © 1992 by American Physiological Society
Both CCK-A and CCK-B/gastrin receptors mediate pepsinogen release in guinea pig gastric glands
C. W. Lin, B. R. Bianchi, T. R. Miller, D. G. Witte and C. A. Wolfram
Pharmaceutical Products Division, Abbott Laboratories, Illinois 60064.
We evaluated the affinity of cholecystokinin octapeptide (CCK-8), gastrin,
and subtype-selective CCK agonists for CCK/gastrin receptors and compared
it with the ability of these peptides to stimulate phosphoinositide (PI)
hydrolysis and pepsinogen release in guinea pig gastric glands. Competitive
binding studies using 125I-labeled Bolton-Hunter-CCK-8 and 125I-gastrin
showed the presence of CCK-B/gastrin receptors in gastric glands and
dispersed chief cells. In contrast, the potency of peptides in stimulating
PI hydrolysis in both gastric glands and dispersed chief cells displayed a
profile similar to CCK-A receptors found in pancreatic acini, i.e., CCK-8 =
A 71378 greater than A 71623 greater than A 70874 much greater than A 72962
= CCK-8 (desulfated) greater than gastrin II greater than gastrin I. In
general, the rank order of potency of peptides for stimulation of PI
hydrolysis correlated well with their ability to stimulate pepsinogen
release. At concentrations greater than 10 microM, efficacies of gastrin I
and II in stimulating pepsinogen release from gastric glands were near 90%
of the maximal activity of CCK-8. The inhibitory potency of MK-329, a
selective CCK-A receptor antagonist, was similar against either CCK-8 (10
nM) or gastrin I (10 microM), except that a minor portion (approximately
30-40%) of gastrin I-induced pepsinogen release was insensitive to MK-329.
The MK-329-insensitive component was inhibited by CI-988, a potent and
selective CCK-B/gastrin receptor antagonist.(ABSTRACT TRUNCATED AT 250
WORDS)
