AJP - Gastrointestinal and Liver Physiology, Vol 256, Issue 2 291-G298, Copyright © 1989 by American Physiological Society
Regulation of bombesin receptors on pancreatic acini by cholecystokinin
M. Younes, S. A. Wank, R. Vinayek, R. T. Jensen and J. D. Gardner
Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892.
When guinea pig pancreatic acini are first incubated with the COOH-terminal
octapeptide of cholecystokinin (CCK-8), washed, and then reincubated with
125I-[Tyr4]bombesin (125I-[Tyr4]BN) there is a significant decrease in
binding of 125I-[Tyr4]BN compared with that observed with pancreatic acini
that have been first incubated with no additions. The CCK-8-induced
decrease in binding is maximal after 90 min of first incubation is
abolished by reducing the temperature of the first incubation from 37 to 4
degrees C or by adding L364,718 to the first incubation and cannot be
reproduced by first incubating acini with A23187, 8-bromoadenosine
3',5'-cyclic monophosphate (8Br-cAMP), 8-bromoadenosine 3',5'-cyclic
monophosphate (8Br-cGMP), or 12-O-tetradecanoylphorbol 13-acetate.
125I-[Tyr4]BN interacts with a single class of receptors on pancreatic
acini, and first incubating acini with CCK-8 decreases the affinity of BN
receptors for BN with no change in the maximal binding capacity. CCK-8 does
not alter the rate at which bound 125I-[Tyr4]BN dissociates from pancreatic
acini; therefore, CCK-8 must alter the rate at which the radiolabeled BN
analogue associates with its receptor. Pancreatic acini possess two classes
of CCK receptors: one has a high affinity for CCK-8; the other has a low
affinity for CCK-8. The dose-response curve for CCK-8-induced inhibition of
binding of 125I-[Tyr4]BN appears to to reflect occupation of low-affinity
CCK receptors by CCK-8.(ABSTRACT TRUNCATED AT 250 WORDS)
