title: Effect of modulation of serotonergic, cholinergic, and nitrergic pathways on murine fundic size and compliance measured by ultrasonomicrometry.
abstract: 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-microm 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, Nomega-nitro-L-arginine, 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, 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.
authors.affiliation: Enteric NeuroScience Program, Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, 200 First St. SW, Rochester, MN 55905, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Xue
authors.forename: G Richard
authors.initials: GR
authors.lastname: Locke
authors.forename: Michael
authors.initials: M
authors.lastname: Camilleri
authors.forename: Jan A J
authors.initials: JA
authors.lastname: Schuurkes
authors.forename: Ann
authors.initials: A
authors.lastname: Meulemans
authors.forename: Bernard J
authors.initials: BJ
authors.lastname: Coulie
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Szurszewski
authors.forename: Gianrico
authors.initials: G
authors.lastname: Farrugia
mesh_terms: D000818:Animals; D001285:Atropine / Q000494:pharmacology; D018723:Bethanechol / Q000494:pharmacology; D002065:Buspirone / Q000494:pharmacology; D005748:Gastric Fundus / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000378:metabolism; D005996:Nitroglycerin / Q000494:pharmacology; D015203:Reproducibility of Results; D012704:Serous Membrane / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D018170:Sumatriptan / Q000494:pharmacology; D014463:Ultrasonography / Q000379:methods*
chemical_list: D018723:Bethanechol; D001285:Atropine; D018170:Sumatriptan; D005996:Nitroglycerin; D002065:Buspirone