Mediation of postprandial pancreatic enzyme secretion has been ascribed mainly to the hormone cholecystokinin (CCK) and to a vagal-vagal reflex that activate cholinergic post-ganglionic neurons in the pancreas. Recently using a rt model we have shown that does of CCK that produce physiological plasma CCK levels stimulate pancreatic enzyme secretion by acting on vagal afferent pathway. CCK-8 receptor antagonist L364,718 inhibited 75% and 80% of the pancreatic secretion stimulated by hyperosmolar NaCI solution and maltose respectively. Large amounts of 5-HT containing cells are found in the proximal duodenal area of the intestine. We hypothesize that 5-HT may be released from the EC cells lining the gut which act as a sensor to test liminal contents in response to luminal stimuli and that this interacts with the cabal afferent nerve endings in the mucosa to evoke pancreatic enzyme secretion via the vagal afferent pathway. We will demonstrate that in the anesthetized and conscious rats, liminal stimuli stimulate pancreatic enzyme secretion via a capsaicin-sensitive afferent vagal pathway. We plan to localize the receptive filed to the duodenal mucosa. Studies utilizing 5-HT receptor blockade and 5-HT neurotoxin will elucidate the role of mucosal released 5-HT in the mediation of these responses. To provide direct neuorphysiological evidence that luminal stimili stimulate vagal afferent pathway, unitary activities of sensory vagal neurons in response to luminal non-CCK dependent stimuli will be recorded. The role of 5-HT in mediating these responses will be investigated. The subclass of vagal afferent fibers which are sensitive to 5-HT will be identified and their sensitivity to CCK tested. Finally, we will delineate the interaction between CCK and non-CCK dependent luminal factors. These studies will have important physiological ramifications and will improve understanding of how non CCK-dependent luminal stimuli act to stimulate pancreatic enzyme secretin.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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General Medicine A Subcommittee 2 (GMA)
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Serrano, Jose
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University of Michigan Ann Arbor
Internal Medicine/Medicine
Schools of Medicine
Ann Arbor
United States
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