Endogenously released opioids mediate meal-induced gastric relaxation via peripheral mu-opioid receptors

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. © 2010 Blackwell Publishing Ltd.