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Am J Physiol Gastrointest Liver Physiol (September 15, 2005). doi:10.1152/ajpgi.00244.2005
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Submitted on May 26, 2005
Accepted on September 7, 2005

Effect of modulation of serotonergic, cholinergic and nitrergic pathways on murine fundic size and compliance measured by ultrasonomicrometry

Lin Xue1, G. Richard Locke1, Michael Camilleri1, Jan A. J. Schuurkes2, Ann Meulemans2, Bernard J. Coulie2, Joseph H. Szurszewski1, and Gianrico Farrugia1*

1 Enteric NeuroScience Program, Mayo Clinic College of Medicine, Rochester, MN, USA
2 Johnson & Johnson Pharmaceutical Research and Development, Beerse, Belgium

* To whom correspondence should be addressed. E-mail: farrugia.gianrico{at}mayo.edu.

Reduced fasting or postprandial gastric volumes have been implicated in the pathophysiology of functional dyspepsia. The mechanisms that underlie the control of gastric fundic volume are incompletely understood, partly because of an inability to accurately measure fundic volume in vivo in small animals. Small animals are useful models to evaluate mechanisms, e.g. in knockout animals. The aim of this study was to determine if an ultrasonometric technique accurately monitors fundic contraction and relaxation in mice in vivo and to determine the effect of modulation of cholinergic, nitrergic and serotonergic pathways on fundic size and compliance in the intact mouse innervated stomach. Two to 4 piezo-electric crystals (diameter 1 mm, 24 µm resolution) were glued to the serosal side of fundus and used to measure distance. Validation studies showed excellent correlation between measured changes and actual changes in distances between crystals and excellent reproducibility. The expected responses to pharmacological modulation with bethanechol and nitroglycerin were demonstrated. Atropine increased the distance between the crystals suggesting a baseline cholinergic regulation of fundic volume. Bethanechol, L-NNA and the 5-HT1B/D agonist sumatriptan decreased the distance between the crystals suggesting fundic contraction. Atropine, nitroglycerin and buspirone caused an increase in intercrystal distance consistent with fundic relaxation. Fundic compliance was investigated by changing intragastric pressure via an implanted catheter. Sumatriptan increased compliance, while buspirone increased the distance between crystals but did not change compliance. The data suggest that ultrasonomicrometry is a useful tool that can reproducibly and accurately measure changes in fundic size and the response to pharmacological agents.




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Am. J. Physiol. Gastrointest. Liver Physiol.Home page
L. Xue, M. Camilleri, G. R. Locke III, J. A. J. Schuurkes, A. Meulemans, B. J. Coulie, J. H. Szurszewski, and G. Farrugia
Serotonergic modulation of murine fundic tone
Am J Physiol Gastrointest Liver Physiol, December 1, 2006; 291(6): G1180 - G1186.
[Abstract] [Full Text] [PDF]




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