title: Inhibitory effect of palmitoylethanolamide on gastrointestinal motility in mice.
abstract: 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 with 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 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.). 3. 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)). 4. 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. 5. 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.
authors.affiliation: Department of Pharmaceutical Sciences, University of Salerno, via Ponte Don Melillo 84084 Fisciano (SA), Italy.
authors.forename: R
authors.initials: R
authors.lastname: Capasso
authors.forename: A A
authors.initials: AA
authors.lastname: Izzo
authors.forename: F
authors.initials: F
authors.lastname: Fezza
authors.forename: A
authors.initials: A
authors.lastname: Pinto
authors.forename: F
authors.initials: F
authors.lastname: Capasso
authors.forename: N
authors.initials: N
authors.lastname: Mascolo
authors.forename: V
authors.initials: V
authors.lastname: Di Marzo
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000577:Amides; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001892:Camphanes / Q000494:pharmacology; D003436:Croton Oil / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D063388:Endocannabinoids; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004983:Ethanolamines; D005769:Gastrointestinal Motility / Q000187:drug effects*; D005772:Gastrointestinal Transit / Q000187:drug effects; D018738:Hexamethonium / Q000494:pharmacology; D007249:Inflammation / Q000139:chemically induced / Q000503:physiopathology; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010169:Palmitic Acids / Q000378:metabolism / Q000494:pharmacology*; D010664:Phenylmethylsulfonyl Fluoride / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000037:antagonists & inhibitors; D000077285:Rimonabant; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D000317:Adrenergic alpha-Antagonists; D000577:Amides; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001892:Camphanes; D063388:Endocannabinoids; D004791:Enzyme Inhibitors; D004983:Ethanolamines; D018733:Nicotinic Antagonists; D010169:Palmitic Acids; D010880:Piperidines; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; C110630:SR 144528; D015016:Yohimbine; D009270:Naloxone; D018738:Hexamethonium; D010664:Phenylmethylsulfonyl Fluoride; C005958:palmidrol; D003436:Croton Oil; D019001:Nitric Oxide Synthase; D000077285:Rimonabant; D019331:NG-Nitroarginine Methyl Ester