Palmitoylethanolamide normalizes intestinal motility in a model of post-inflammatory accelerated transit: involvement of CB₁ receptors and TRPV1 channels.

Abstract

BACKGROUND AND PURPOSE:

Palmitoylethanolamide (PEA), a naturally occurring acylethanolamide chemically related to the endocannabinoid anandamide, interacts with targets that have been identified in peripheral nerves controlling gastrointestinal motility, such as cannabinoid CB1 and CB2 receptors, TRPV1 channels and PPARα. Here, we investigated the effect of PEA in a mouse model of functional accelerated transit which persists after the resolution of colonic inflammation (post-inflammatory irritable bowel syndrome).

EXPERIMENTAL APPROACH:

Intestinal inflammation was induced by intracolonic administration of oil of mustard (OM). Mice were tested for motility and biochemical and molecular biology changes 4 weeks later. PEA, oleoylethanolamide and endocannabinoid levels were measured by liquid chromatography-mass spectrometry and receptor and enzyme mRNA expression by qRT-PCR.

KEY RESULTS:

OM induced transient colitis and a functional post-inflammatory increase in upper gastrointestinal transit, associated with increased intestinal anandamide (but not 2-arachidonoylglycerol, PEA or oleoylethanolamide) levels and down-regulation of mRNA for TRPV1 channels. Exogenous PEA inhibited the OM-induced increase in transit and tended to increase anandamide levels. Palmitic acid had a weaker effect on transit. Inhibition of transit by PEA was blocked by rimonabant (CB1 receptor antagonist), further increased by 5'-iodoresiniferatoxin (TRPV1 antagonist) and not significantly modified by the PPARα antagonist GW6471.

CONCLUSIONS AND IMPLICATIONS:

Intestinal endocannabinoids and TRPV1 channel were dysregulated in a functional model of accelerated transit exhibiting aspects of post-inflammatory irritable bowel syndrome. PEA counteracted the accelerated transit, the effect being mediated by CB1 receptors (possibly via increased anandamide levels) and modulated by TRPV1 channels.

• Authors: Raffaele Capasso, Pierangelo Orlando, Ester Pagano, Teresa Aveta, Lorena Buono, Francesca Borrelli, Vincenzo Di Marzo, Angelo A Izzo
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 171 Issue 17 Pg. 4026-37 (Sep 2014) ISSN: 1476-5381 [Electronic] England
• PMID: 24818658 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 The British Pharmacological Society.

Chemical References

• Amides
• Ethanolamines
• Palmitic Acids
• Piperidines
• Plant Oils
• Pyrazoles
• RNA, Messenger
• Receptor, Cannabinoid, CB1
• TRPV Cation Channels
• palmidrol
• Rimonabant
• mustard oil

Topics

• Amides
• Animals
• Colitis (chemically induced, drug therapy, metabolism)
• Disease Models, Animal
• Ethanolamines (administration & dosage, antagonists & inhibitors, pharmacology)
• Gastrointestinal Motility (drug effects)
• Inflammation (chemically induced, drug therapy, metabolism)
• Injections, Intraperitoneal
• Irritable Bowel Syndrome (chemically induced, drug therapy, metabolism)
• Male
• Mice
• Mice, Inbred ICR
• Mustard Plant
• Palmitic Acids (administration & dosage, antagonists & inhibitors, pharmacology)
• Piperidines (pharmacology)
• Plant Oils (administration & dosage)
• Pyrazoles (pharmacology)
• RNA, Messenger (genetics, metabolism)
• Receptor, Cannabinoid, CB1 (antagonists & inhibitors, metabolism)
• Rimonabant
• TRPV Cation Channels (antagonists & inhibitors, genetics, metabolism)