The major objectives of this research proposal are: (1) to elucidate the physiology of (a) esophageal peristalsis and (b) lower esophageal sphincter (LES) tone and relaxation; (2) to identify the nature of the neurotransmitters involved in esophageal reflex activities; (3) to explore the pharmacology of esophageal body and LES; and (4) to arrive at a synthesis of structure-function relationships by complementing these studies with morphological investigations. These studies in the animal model will be extended to diseased tissues obtained at surgery from patients with esophageal disorders. We will use a number of different in vivo and in vitro systems to record membrane potentials by indirect (suction electrodes) and direct (single cell intracellular) methods, so as to learn about the nature of the neural reflexes in both intact animals as well as in muscle strips. These studies will also extend to the morphology and morphometry of the myenteric plexus, using our recently-developed rapid non-silver method and our technique of ganglionic isolation. An immunocytochemical approach will provide valuable histophysiological insights to supplement morphological findings. Ganglionic isolation will also be used to investigate ultrastructure with scanning and transmission electron microscopy of the myenteric plexus from various segments of the esophagus. Morphologic and physiologic correlations of neural control of esophageal function will thus be made. These studies will advance our understading of the physiology of esophageal motility and the pathophysiology of esophageal motor disorders. This understanding may provide avenues for rational treatment of these disorders. Moreover, lessons learned from these studies of the esophagus may have wider implications in physiology and pathophysiology of the autonomic nervous system, particularly that of the gastrointestinal tract.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37DK031092-10
Application #
3483596
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1981-09-01
Project End
1991-04-30
Budget Start
1990-05-01
Budget End
1991-04-30
Support Year
10
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02215
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Szymanski, Pawel T; Szymanska, Grazyna; Goyal, Raj K (2002) Differences in calmodulin and calmodulin-binding proteins in phasic and tonic smooth muscles. Am J Physiol Cell Physiol 282:C94-C104
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