Pancreatic exocrine secretion is preciously regulated by hormonal and neural mechanisms. Although at least half of pancreatic exocrine secretion is controlled by neural mechanisms involving the vagus nerve, little is known about how it is regulated. The applicant's long term objective is to understand mechanisms of feedback control of centrally stimulated pancreatic secretion. Several recent discoveries from this laboratory and others have led us to hypothesize that he hormones pancreatic polypeptide (PP) and peptide YY (PYY) play an important role in feedback control of central (i.e. vagally mediated) pancreatic secretion: however, the mechanism is unknown. We hypothesize that a major point of control is the portion of the dorsal vagal complex that is outside the blood-brain barrier where these peptides have high affinity receptor and can act directly.
Our aim i s to systematically study centrally stimulated pancreatic secretion focusing on the dorsal vagal complex through microinfusion techniques and receptor autoradiography. An understanding of these mechanisms may be very important for defining basic principles of gut-brain interactions and regulations. These studies may lead to new theories on the etiology of various pancreatic disorders including idiopathic and a alcoholic pancreatitis. In addition, understanding these mechanism may lead to new therapies for resting the pancreas in acute pancreatitis or treating the cause of pain in chronic pancreatitis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29DK045781-02
Application #
2145030
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1993-12-15
Project End
1998-11-30
Budget Start
1994-12-01
Budget End
1995-11-30
Support Year
2
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
053785812
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Deng, Xiaoying; Wood, Paul G; Eagon, Patricia K et al. (2005) Rapid adaptation of pancreatic exocrine function to short-term alcohol feeding in rats. Pancreatology 5:183-95
Boggiano, M M; Chandler, P C; Oswald, K D et al. (2005) PYY3-36 as an anti-obesity drug target. Obes Rev 6:307-22
Deng, Xiaoying; Wood, Paul G; Eagon, Patricia K et al. (2004) Chronic alcohol-induced alterations in the pancreatic secretory control mechanisms. Dig Dis Sci 49:805-19
Deng, X; Guarita, D R; Pedroso, M R et al. (2001) Area postrema lesion alters the effects of peptide YY on 2-DG-stimulated pancreatic exocrine secretion. Dig Dis Sci 46:2460-9
Deng, X; Guarita, D R; Wood, P G et al. (2001) PYY potently inhibits pancreatic exocrine secretion mediated through CCK-secretin-stimulated pathways but not 2-DG-stimulated pathways in awake rats. Dig Dis Sci 46:156-65
Deng, X; Guarita, D R; Pedroso, M R et al. (2001) PYY inhibits CCK-stimulated pancreatic secretion through the area postrema in unanesthetized rats. Am J Physiol Regul Integr Comp Physiol 281:R645-53
Deng, X; Wood, P G; Sved, A F et al. (2001) The area postrema lesions alter the inhibitory effects of peripherally infused pancreatic polypeptide on pancreatic secretion. Brain Res 902:18-29
Guarita, D R; Deng, X; Huh, Y B et al. (2000) PYY regulates pancreatic exocrine secretion through multiple receptors in the awake rat. Dig Dis Sci 45:1696-702
Ulrich 2nd, C D; Wood, P; Hadac, E M et al. (1998) Cellular distribution of secretin receptor expression in rat pancreas. Am J Physiol 275:G1437-44
Seymour, N E; Spector, S A; Andersen, D K et al. (1998) Overexpression of hepatic pancreatic polypeptide receptors in chronic pancreatitis. J Surg Res 76:47-52

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