Pancreatic polypeptide [PP] is released from pancreatic endocrine cells following feeding. The release of this peptide from the pancreas:, produces a reduction in pancreatic exocrine secretion, as well as changes in gastrointestinal secretion and motility. PP action on digestion has been difficult to explain in that its acute actions on digestive functions are not direct. Intact vagal efferent innervation is required for PP effects, a fact that lead to speculation that PP may control vagal efferent projections to the gut and pancreas through endocrine action on brainstem structures. This view recently received significant reinforcement with the finding that the dorsal vagal complex in the medulla contains a high concentration of saturable and specific receptors for PP. Thus, pancreatic polypeptide [PP] may represent a unique digestive endocrine feedback control signal which directly regulates the excitability of vago-vagal reflex circuits to control digestive functions. We plan to apply two separate methods to test this hypothesis directly. First, we will apply PP directly to the dorsal vagal complex using quantitative micropressure injection techniques. This will establish if PP can act via vago-vagal reflex circuits to produce measurable changes in gastrointestinal and/or pancreatic functions. Studies will be performed in both anesthetized and acute, awake preparations. Next, we will determine how PP affects the function of neurophysiologically identified neuronal components of vago-vagal circuits in the brainstem in the intact, anesthetized rat. These studies will determine how PP acts on individual identifiable neuronal components of digestion control reflexes. Together, these studies will provide an indication of how this unique pancreatic endocrine hormone can control an array of digestive functions by acting on vagal circuits in the brainstem.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS030803-01
Application #
3417727
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1992-07-01
Project End
1995-06-30
Budget Start
1992-07-01
Budget End
1993-06-30
Support Year
1
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Ohio State University
Department
Type
Schools of Medicine
DUNS #
098987217
City
Columbus
State
OH
Country
United States
Zip Code
43210
McTigue, D M; Hermann, G E; Rogers, R C (1997) Effect of pancreatic polypeptide on rat dorsal vagal complex neurons. J Physiol 499 ( Pt 2):475-83
Chen, C H; Rogers, R C (1997) Peptide YY and the Y2 agonist PYY-(13-36) inhibit neurons of the dorsal motor nucleus of the vagus. Am J Physiol 273:R213-8
Chen, C H; Stephens Jr, R L; Rogers, R C (1997) PYY and NPY: control of gastric motility via action on Y1 and Y2 receptors in the DVC. Neurogastroenterol Motil 9:109-16
Chen, C H; Rogers, R C; Stephens Jr, R L (1996) Intracisternal injection of peptide YY inhibits gastric emptying in rats. Regul Pept 61:95-8
Rogers, R C; McTigue, D M; Hermann, G E (1996) Vagal control of digestion: modulation by central neural and peripheral endocrine factors. Neurosci Biobehav Rev 20:57-66
Rogers, R C; McTigue, D M; Hermann, G E (1995) Vagovagal reflex control of digestion: afferent modulation by neural and ""endoneurocrine"" factors. Am J Physiol 268:G1-10
Hermann, G; Rogers, R C (1995) Tumor necrosis factor-alpha in the dorsal vagal complex suppresses gastric motility. Neuroimmunomodulation 2:74-81
McTigue, D M; Chen, C H; Rogers, R C et al. (1995) Intracisternal rat pancreatic polypeptide stimulates gastric emptying in the rat. Am J Physiol 269:R167-72
Chen, C H; Rogers, R C (1995) Central inhibitory action of peptide YY on gastric motility in rats. Am J Physiol 269:R787-92
Rogers, R C; McCann, M J (1993) Intramedullary connections of the gastric region in the solitary nucleus: a biocytin histochemical tracing study in the rat. J Auton Nerv Syst 42:119-30

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