The long-term objective of this work is to understand the mechanism of action of GRP in regulating stomach function. A major specific aim of this proposal is to determine if the binding site for GRP and related peptides on canine antral gastrin cells in the stomach is the receptor mediating the effects of GRP- stimulated gastrin secretion and gastrin cell hyperplasia. A second hypothesis to be tested is that the canine antral gastrin cell GRP receptor represents a new class of GRP receptor. A third hypothesis that will be tested by these studies is that a major mechanism of chronic antral gastrin cell hyperfunction is dynamic change in the number or affinity of GRP receptors on gastrin cells. These hypotheses will be tested by determination of the affinities and specificities of gastrin cell GRP receptors for GRP, bombesin, and related peptides both with regard to specific binding of radioiodinated peptides and with regard to stimulation of gastrin secretion and gastrin cell hyperplasia. Various pathways leading to gastrin cell hyperfunction (surgical and chemical achlorhydria, vagotomy, chronic GRP injections) will be used to test the hypothesis that changing gastrin cell GRP receptor number mediates gastrin cell responses to these agents and treatments. The GRP receptor on canine antral gastrin cells, canine antral smooth muscle cells, rat brain membranes, and rat pancreatic acini will be crosslinked to obtain biochemical evidence of the molecular weight of various GRP receptors and to aid evaluation of the hypothesis that gastrin cells possess a novel GRP receptor. It is possible that chronic hyperactivity of GRP nerves in the gastric antrum up-regulates gastrin cell GRP receptors which leads in turn to increased basal plasma gastrin and exaggerated food-stimulated gastrin responses found in patients with treatment-resistant duodenal ulcer disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
1R01DK040260-01
Application #
3240446
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1987-09-01
Project End
1990-08-31
Budget Start
1987-09-01
Budget End
1988-08-31
Support Year
1
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Duke University
Department
Type
Schools of Medicine
DUNS #
071723621
City
Durham
State
NC
Country
United States
Zip Code
27705
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