Inhibitory effect of palmitoylethanolamide on gastrointestinal motility in mice

We have studied the effect of palmitoylethanolamide (PEA, 2.5 – 30 mg kg −1 , i.p.) on upper gastrointestinal transit in control mice and in mice with chronic intestinal inflammation induced by croton oil. PEA significantly and dose‐dependently decreased intestinal transit. The inhibitory effect of PEA (10 mg kg −1 ) was not modified by the cannabinoid CB 1 receptor antagonist SR141716A (0.3 mg kg −1 , i.p.), the cannabinoid CB 2 receptor antagonist SR144528 (1 mg kg −1 , i.p.), N G ‐nitro‐ L ‐arginine methyl ester ( L ‐NAME, 25 mg kg −1 , i.p.), yohimbine (1 mg kg −1 , i.p.), naloxone (2 mg kg −1 , i.p.) or hexamethonium (1 mg kg −1 , i.p.). PEA levels were significantly decreased in the small intestine of croton oil‐treated mice. In these animals, PEA also inhibited motility and this effect was not counteracted by SR141716A (0.3 mg kg −1 ), or SR144528 (1 mg kg −1 ). Pre‐treatment of mice with the amidase inhibitor phenylmethyl sulphonil fluoride (PMSF, 30 mg kg −1 , i.p.) did not modify the inhibitory effect of PEA, either in control or in mice with inflammation. It is concluded that PEA inhibits intestinal motility with a peripheral mechanism independent from cannabinoid receptor activation. The decreased levels of PEA in croton oil‐treated might contribute, at least in part, to the exaggerated transit observed during chronic intestinal inflammation.British Journal of Pharmacology (2001) 134 , 945–950; doi: 10.1038/sj.bjp.0704339