Effect of selective CCK1 receptor antagonism on accommodation and tolerance of intestinal gas in functional gut disorders

J Gastroenterol Hepatol. 2016 Feb;31(2):288-93. doi: 10.1111/jgh.13177.

Abstract

Background: Participants with functional gut disorders develop gas retention and symptoms in response to intestinal gas loads that are well tolerated by healthy subjects. To determine the role of cholecystokinin (CCK1 ) receptors on gas transit and tolerance in women with functional gut disorders.

Methods: In 12 healthy women, and 24 women with functional gut disorders (12 dyspepsia and 12 constipation-predominant irritable bowel syndrome) gas was infused into the jejunum at 12 mL/min for 3 h with simultaneous duodenal lipid infusion (intralipid 1 kcal/min), while measuring anal gas evacuation and abdominal symptoms on a 0-6 score scale. Triple-blind paired studies during iv infusion of dexloxiglumide (2.5 mg/kg bolus plus 5 mg/kg h continuous infusion), a selective CCK1 inhibitor, or saline (control) were performed in random order.

Results: During saline infusion participants with functional gut disorders developed significantly greater gas retention and abdominal symptoms than healthy subjects (394 ± 40 mL vs 265 ± 35 mL and 2.8 ± 0.3 vs 1.9 ± 0.4 highest abdominal symptom score, respectively; P < 0.05 for both). Dexloxiglumide increased gas retention in both groups (514 ± 35 mL and 439 ± 60 mL, respectively; P = 0.033 vs saline for both); however, despite the larger retention, dexloxiglumide reduced abdominal symptoms (2.3 ± 0.2 score and 0.8 ± 0.3 score, respectively; P = 0.05 vs saline for both). Post-hoc analysis showed that, the decrease in abdominal symptoms was more pronounced in those participants with functional gut disorders with higher basal abdominal symptoms than in the rest (P = 0.037).

Conclusion: Inhibition of CCK1 receptors by dexloxiglumide increases intestinal gas retention and reduces abdominal symptoms in response to by intestinal gas loads. European Clinical Trials Database (EudraCT 2005-003338-16).

Keywords: CCK1 receptor; cholecystokinin; dexloxiglumide; functional gut symptoms; intestinal gas; intestinal motility; intestinal sensitivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Dyspepsia / metabolism*
  • Dyspepsia / physiopathology*
  • Female
  • Flatulence / drug therapy
  • Flatulence / metabolism*
  • Flatulence / physiopathology*
  • Gases / metabolism*
  • Gastrointestinal Transit* / drug effects
  • Humans
  • Irritable Bowel Syndrome / metabolism*
  • Irritable Bowel Syndrome / physiopathology*
  • Middle Aged
  • Pentanoic Acids / pharmacology*
  • Pentanoic Acids / therapeutic use
  • Receptors, Cholecystokinin / antagonists & inhibitors*
  • Receptors, Cholecystokinin / physiology*
  • Treatment Outcome
  • Young Adult

Substances

  • Gases
  • Pentanoic Acids
  • Receptors, Cholecystokinin
  • dexloxiglumide

Associated data

  • EudraCT/2005-003338-16