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: R Capasso, A A Izzo, F Fezza, A Pinto, F Capasso, N Mascolo, V Di Marzo
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 134 Issue 5 Pg. 945-50 (Nov 2001) ISSN: 0007-1188 [Print] England
• PMID: 11682441 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adrenergic alpha-Antagonists
• Amides
• Anti-Inflammatory Agents, Non-Steroidal
• Camphanes
• Endocannabinoids
• Enzyme Inhibitors
• Ethanolamines
• Nicotinic Antagonists
• Palmitic Acids
• Piperidines
• Pyrazoles
• Receptors, Cannabinoid
• Receptors, Drug
• SR 144528
• Yohimbine
• Naloxone
• Hexamethonium
• Phenylmethylsulfonyl Fluoride
• palmidrol
• Croton Oil
• Nitric Oxide Synthase
• Rimonabant
• NG-Nitroarginine Methyl Ester

Topics

• Adrenergic alpha-Antagonists (pharmacology)
• Amides
• Animals
• Anti-Inflammatory Agents, Non-Steroidal (pharmacology)
• Camphanes (pharmacology)
• Croton Oil (administration & dosage)
• Dose-Response Relationship, Drug
• Endocannabinoids
• Enzyme Inhibitors (pharmacology)
• Ethanolamines
• Gastrointestinal Motility (drug effects)
• Gastrointestinal Transit (drug effects)
• Hexamethonium (pharmacology)
• Inflammation (chemically induced, physiopathology)
• Intestine, Small (drug effects, metabolism, physiopathology)
• Male
• Mice
• Mice, Inbred ICR
• NG-Nitroarginine Methyl Ester (pharmacology)
• Naloxone (pharmacology)
• Nicotinic Antagonists (pharmacology)
• Nitric Oxide Synthase (antagonists & inhibitors)
• Palmitic Acids (metabolism, pharmacology)
• Phenylmethylsulfonyl Fluoride (pharmacology)
• Piperidines (pharmacology)
• Pyrazoles (pharmacology)
• Receptors, Cannabinoid
• Receptors, Drug (antagonists & inhibitors)
• Rimonabant
• Yohimbine (pharmacology)