P Janssen1, H Pottel, R Vos, J Tack. 1. Department of Internal Medicine, University Hospital Gasthuisberg, University of Leuven, Belgium. pieter.janssen@med.kuleuven.be
Abstract
BACKGROUND: The centrally acting mu-opioid receptor antagonist naloxone inhibits meal-induced gastric accommodation. AIM: To study the role of peripheral mu-opioid receptors in the regulation of gastric tone and food intake by comparing the effects of naloxone with the peripherally restricted mu-opioid receptor antagonist methylnaltrexone. METHODS:Methylnaltrexone (12 mg s.c.), naloxone (20 μg/kg/h intravenous infusion after 0.4 mg bolus) and placebo were studied in 23 healthy volunteers. Gastric volume was recorded using an intragastric bag held at constant pressure connected to a barostat, with administration of a nutrient drink after 30 min. Pressure in the stomach was measured during intragastric nutrient drink infusion until the volunteers scored maximal satiation. RESULTS:Methylnaltrexone inhibited significantly the volume increase after food intake as assessed with the barostat (P < 0.01). During nutrient drink infusion the intragastric pressure significantly decreased as compared with the preprandial pressure after placebo treatment. Both methylnaltrexone and naloxone significantly inhibited this intragastric pressure decrease (P < 0.001 and P < 0.05, respectively). Volunteers scored maximal satiation after 979 ± 96, 958 ± 84 and 1124 ± 107 mL nutrient drink infused (for naloxone, methylnaltrexone and placebo treatment, respectively; P < 0.05). CONCLUSIONS: These results indicate that endogenous opioids mediate gastric accommodation and satiation via peripheral mu-opioid receptors. Effects were less pronounced after naloxone treatment, which indicates that centrally involved mu-opioid receptors mediate an opposing effect.
RCT Entities:
BACKGROUND: The centrally acting mu-opioid receptor antagonist naloxone inhibits meal-induced gastric accommodation. AIM: To study the role of peripheral mu-opioid receptors in the regulation of gastric tone and food intake by comparing the effects of naloxone with the peripherally restricted mu-opioid receptor antagonist methylnaltrexone. METHODS:Methylnaltrexone (12 mg s.c.), naloxone (20 μg/kg/h intravenous infusion after 0.4 mg bolus) and placebo were studied in 23 healthy volunteers. Gastric volume was recorded using an intragastric bag held at constant pressure connected to a barostat, with administration of a nutrient drink after 30 min. Pressure in the stomach was measured during intragastric nutrient drink infusion until the volunteers scored maximal satiation. RESULTS:Methylnaltrexone inhibited significantly the volume increase after food intake as assessed with the barostat (P < 0.01). During nutrient drink infusion the intragastric pressure significantly decreased as compared with the preprandial pressure after placebo treatment. Both methylnaltrexone and naloxone significantly inhibited this intragastric pressure decrease (P < 0.001 and P < 0.05, respectively). Volunteers scored maximal satiation after 979 ± 96, 958 ± 84 and 1124 ± 107 mL nutrient drink infused (for naloxone, methylnaltrexone and placebo treatment, respectively; P < 0.05). CONCLUSIONS: These results indicate that endogenous opioids mediate gastric accommodation and satiation via peripheral mu-opioid receptors. Effects were less pronounced after naloxone treatment, which indicates that centrally involved mu-opioid receptors mediate an opposing effect.
Authors: R H Hunt; M Camilleri; S E Crowe; E M El-Omar; J G Fox; E J Kuipers; P Malfertheiner; K E L McColl; D M Pritchard; M Rugge; A Sonnenberg; K Sugano; J Tack Journal: Gut Date: 2015-09-04 Impact factor: 23.059