Although peripheral autonomic ganglia are important in the maintenance of normal gastrointestinal functions, the mechanisms of ganglion cell excitability, transmission and interconnectedness between the ganglia and their target organs are as yet imperfectly understood. The overall objectives of this proposal are: (1) to elucidate in guinea pigs, mice and cats, the range of mechanisms by which prevertebral ganglia control motor activity of the colon; and (2) the basic electrophysiology underlying excitability and chemical transmission in intrapancreatic ganglia, a hitherto unexplored area of gastroenterology. Investigations in the inferior mesenteric ganglion (IMG) are designed to answer the following questions. First, do axon collaterals of spinal afferent capsaicin- sensitive nerves mediate a peripheral, visceral sensory-autonomic reflex by releasing SP-, NKA- and CGRP-LI in the IMG during colonic distension? Second, do central preganglionic peptide containing nerves synapsing in the IMG gate distension-induced release of SP-, NKA- and CGRP-LI? Third, do colonic myenteric VIP-containing neurons projecting to sympathetic neurons in the IMG release VIP during colonic distension? Fourth, what is the functional importance of GABA-containing colonic afferents? And, fifth, what is the nature of the colonic mechanoreceptor unit which mediates peripheral reflex activity and where is it located in the colon wall? Investigations in intrapancreatic ganglia are designed to answer the following questions. First, are there differences in electrophysiological characteristics between intrapancreatic neurons in the head and tail regions of the pancreas? Second, do CCK peptides, VIP and 5-HT participate in intrapancreatic synaptic events? And third, are gastroduodenal myenteric neurons that send their axonal projections to intrapancreatic ganglia activated by distension and/or intraluminal acidity? Intracellular electrophysiological techniques will be combined with radioimmunological, chromatographic and quantitative radiodensitometric thin-layer chromatographic techniques. It is hoped that these studies will shed light on disorders of colonic motility in humans. The presence of functional GABA receptors in peripheral autonomic ganglia makes it very likely that anxiolytic drugs like the benzodiazepines very likely affect gastrointestinal motility in patients. Studies on intrapancreatic ganglia will provide a better understanding of their physiological importance thereby providing insights into pancreatic function of the transplanted organ.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK017632-18
Application #
3225819
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1977-07-01
Project End
1995-11-30
Budget Start
1991-12-01
Budget End
1992-11-30
Support Year
18
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
City
Rochester
State
MN
Country
United States
Zip Code
55905
Matsuda, Nilce Mitiko; Miller, Steven M; Szurszewski, Joseph H (2010) Heme-oxygenase-2 immunolabelling in pig jejunum. Acta Histochem 112:402-6
Vernino, Steven; Ermilov, Leonid G; Sha, Lei et al. (2004) Passive transfer of autoimmune autonomic neuropathy to mice. J Neurosci 24:7037-42
Sha, Lei; Miller, Steven M; Szurszewski, Joseph H (2004) Morphology and electrophysiology of neurons in dog paraventricular nucleus: in vitro study. Brain Res 1010:95-107
Ermilov, Leonid G; Schmalz, Philip F; Miller, Steven M et al. (2004) PACAP modulation of the colon-inferior mesenteric ganglion reflex in the guinea pig. J Physiol 560:231-47
Miller, Steven M; Szurszewski, J H (2003) Circumferential, not longitudinal, colonic stretch increases synaptic input to mouse prevertebral ganglion neurons. Am J Physiol Gastrointest Liver Physiol 285:G1129-38
Ermilov, L G; Miller, S M; Schmalz, P F et al. (2003) Morphological characteristics and immunohistochemical detection of nicotinic acetylcholine receptors on intestinofugal afferent neurones in guinea-pig colon. Neurogastroenterol Motil 15:289-98
Miller, S M; Szurszewski, J H (2002) Relationship between colonic motility and cholinergic mechanosensory afferent synaptic input to mouse superior mesenteric ganglion. Neurogastroenterol Motil 14:339-48
Sha, L; Westerlund, J; Szurszewski, J H et al. (2001) Amplitude modulation of pulsatile insulin secretion by intrapancreatic ganglion neurons. Diabetes 50:51-5
Ermilov, L G; Miller, S M; Schmalz, P F et al. (2000) The three-dimensional structure of neurons in the guinea pig inferior mesenteric and pelvic hypogastric ganglia. Auton Neurosci 83:116-26
Miller, S M (2000) Control of peripheral sympathetic prevertebral ganglion neurones by colonic mechanosensory afferents. Gut 47 Suppl 4:iv28-9; discussion iv36

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