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NEUROREGULATION AND MOTILITY

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

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

Submitted 26 May 2005 ; accepted in final form 7 September 2005

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 whether 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 four piezoelectric 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, N-nitro-L-arginine, and the 5-HT_1B/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, whereas 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.

ultrasound; smooth muscle; gastric fundus; serotonin

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				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]