Title

Regulation of bombesin receptors on pancreatic acini by cholecystokinin

Document Type

Journal Article

Publication Date

1-1-1989

Journal

American Journal of Physiology - Gastrointestinal and Liver Physiology

Volume

256

Issue

2

Abstract

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°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-bromoguanosine 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 reflect occupation of low-affinity CCK receptors by CCK-8. Finally, although first incubating acini with CCK-8 reduces the affinity of BN receptors for BN, it reduces the maximal response for BN-stimulated enzyme secretion with no detectable shift in the dose-response curve for BN-stimulated enzyme secretion. Thus the effect of CCK-8 on the affinity of the BN receptor can be dissociated from the effect of CCK-8 on BN-stimulated enzyme secretion.

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