title: Prokinetic effects of large-dose lubiprostone on gastrointestinal transit in dogs and its mechanisms.
abstract: OBJECTIVE
  To systemically explore effects of large dose of lubiprostone on gastrointestinal (GI) transit and contractions and its safety in dogs.
  
  
  METHODS
  12 healthy dogs were studied. 6 dogs were operated to receive duodenal cannula and colon cannula and the other 6 dogs received gastric cannula. Lubiprostone was orally administrated at a dose of 24 µg or 48 µg 1 hr prior to the experiments. Gastric emptying (GE) of solids and small bowel transit were evaluated by collecting the effluents from the duodenal cannula and from the colon cannula. Gastric accommodation was measured by barostat. Gastric and intestinal contractions were by manometry. Colon transit was by X-ray pictures.
  
  
  RESULTS
  1) Lubiprostone 48 µg not 24 µg accelerated GE. Atropine could block the effect; 2) Average motility index (MI) of gastric antrum in lubiprostone 48 µg session was significantly higher in both fasting state (P = 0.01) and fed state (P = 0.03). Gastric accommodation was not significantly different; 3) Lubiprostone 48 µg accelerated small bowel and colon transit. Atropine could block the effect on small bowel transit; 4) Lubiprostone 48 µg increased postprandial small bowel MI (P = 0.0008) and colon MI (P = 0.002). 5) No other adverse effects except for diarrhea were observed.
  
  
  CONCLUSIONS
  Acute administration of lubiprostone at a dose of 48 µg accelerates GI motility and enhances GI contractions in the postprandial state. The findings suggest that lubiprostone may have an indirect prokinetic effects on the GI tract and vagal activity may be involved. Lubiprostone may be safely used.
authors.affiliation: Division of Gastroenterology, University of Texas Medical Branch Galveston, Texas ; Department of Gastroenterology, Union Hospital, Huazhong University of Science and Technology Wuhan, Hubei, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Song
authors.affiliation: Division of Gastroenterology, University of Texas Medical Branch Galveston, Texas.
authors.forename: Jieyun
authors.initials: J
authors.lastname: Yin
authors.affiliation: Ningbo Pace Translational Medical Research Center Beilun, Ningbo, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Xu
authors.affiliation: Division of Gastroenterology, University of Texas Medical Branch Galveston, Texas ; Ningbo Pace Translational Medical Research Center Beilun, Ningbo, China.
authors.forename: Jiande
authors.initials: J
authors.lastname: Chen
keywords: Constipation; gastric accommodation; gastrointestinal motility; lubiprostone