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Keywords:

  • enteric nervous system;
  • intestinal motility;
  • oleoylethanolamide;
  • peroxisome proliferator-activated receptor alpha;
  • stress enhanced motility

Abstract  Oleoylethanolamide (OEA) is an endogenous lipid produced in the intestine that mediates satiety by activation of peroxisome proliferator-activated receptor alpha (PPARα). OEA inhibits gastric emptying and intestinal motility, but the mechanism of action remains to be determined. We investigated whether OEA inhibits intestinal motility by activation of PPARα. PPARα immunoreactivity was examined in whole mount preparations of mouse gastrointestinal (GI) tract. The effect of OEA on motility was assessed in wildtype, PPARα, cannabinoid CB1 receptor and CB2 receptor gene-deficient mice and in a model of accelerated GI transit. In addition, the effect of OEA on motility was assessed in mice injected with the PPARα antagonist GW6471, transient receptor potential vanilloid 1 antagonist SB366791 or the glucagon-like peptide 1 antagonist exendin-3(9-39) amide. PPARα immunoreactivity was present in neurons in the myenteric and submucosal plexuses throughout the GI tract. OEA inhibited upper GI transit in a dose-dependent manner, but was devoid of an effect on whole gut transit or colonic propulsion. OEA-induced inhibition of motility was still present in PPARα, CB1 and CB2 receptor gene-deficient mice and in the presence of GW6471, SB366791 and exendin-3(9-39) amide, suggesting neither PPARα nor the cannabinoids and other likely receptors are involved in mediating the effects of OEA. OEA blocked stress-induced accelerated upper GI transit at a dose that had no effect on physiological transit. We show that PPARα is found in the enteric nervous system, but our results suggest that PPARα is not involved in the suppression of motility by OEA.