EXTRINSIC CONTROL OF GASTROINTESTINAL MOTILITY

  • Szurszewski, Joseph H, (PI)

Project: Research project

Project Details

Description

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.
StatusFinished
Effective start/end date7/1/776/30/07

Funding

  • National Institutes of Health: $257,186.00
  • National Institutes of Health
  • National Institutes of Health: $257,186.00
  • National Institutes of Health: $225,759.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $257,186.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $257,186.00
  • National Institutes of Health: $257,186.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

ASJC

  • Medicine(all)

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