Inhibitory effect of palmitoylethanolamide on gastrointestinal motility inmice

1. 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 wit h chronic intestinal inflammation induced by croton oil. 2. PEA significantly and dose-dependently decreased intestinal transit. The inhibitory effect of PEA (10 mg kg(-1)) was not modified by the cannabinoi d CB1 receptor antagonist SR141716A (0.3 mg kg(-1), i.p.), the cannabinoid CB2 receptor antagonist SR144528 (I mg kg(-1), i.p.), N-G-nitro-L-arginine methyl ester (L-NAME, 25 mg kg(-1), i.p.), yohimbine (I mg kg(-1), i.p.), n aloxone (2 mg kg(-1), i.p.) or hexamethonium. (1 mg kg(-1), i.p.). 3 PEA levels were significantly decreased in the small intestine of croton oil-treated mice. In these animals, PEA also inhibited motility and this ef fect was not counteracted by SR141716A (0.3 mg kg(-1)), or SR144528 (I mg k g(-1)). 4 Pre-treatment of mice with the amidase inhibitor phenylmethyl sulphonil f luoride (PMSF, 30 mg kg(-1), i.p.) did not modify the inhibitory effect of PEA, either in control or in mice with inflammation. 5 It is concluded that PEA inhibits intestinal motility with a peripheral m echanism independent from cannabinoid receptor activation. The decreased le vels of PEA in croton oil-treated might contribute, at least in part, to th e exaggerated transit observed during chronic intestinal inflammation.