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, i.e. cannabinoid (CB1 and CB2 ) receptors, transient receptor potential vanilloid type-1 (TRPV1), and peroxisomal proliferator activated receptor α (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(IBS)-like] EXPERIMENTAL APPROACH: Intestinal inflammation was induced by intracolonic administration of oil of mustard (OM). Mice were tested for motility and biochemical/molecular biology changes four weeks later. Palmitoylethanolamide, oleoylethanolamide and endocannabinoid levels were measured by chromatography-mass spectrometry, and receptor and enzyme mRNA expression by quantitative reverse transcription-PCR.

KEY RESULTS:

OM induced transient colitis and a functional post-inflammatory increase in upper gastrointestinal transit which was associated to elevation of intestinal anandamide (but not 2-arachidonoylglycerol, palmitoylethanolamide or oleoylethanolamide) levels and down-regulation of TRPV1 mRNA expression. Exogenous ultramicronized palmitoylethanolamide counteracted OM-induced increase in transit and tended to increase anandamide levels. Palmitic acid had a weaker effect on transit. The inhibitory effect of palmitoylethanolamide on transit was counteracted by rimonabant (CB1 receptor antagonist), further increased by 5′-iodoresiniferatoxin (I-RTX, TRPV1 antagonist) and not significantly modified by the PPARα antagonist GW6471.

CONCLUSIONS AND IMPLICATIONS:

Intestinal endocannabinoid and TRPV1 dysregulation were detected in a functional model of accelerated transit modeling some aspects of post-inflammatory IBS. Palmitoylethanolamide counteracted the accelerated transit, the effect being mediated by CB1 receptors (possibly via increased anandamide levels) and modulated by TRPV1 channels.
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PMID:

 

24818658

 

[PubMed – as supplied by publisher]