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Palmitoylethanolamide normalizes intestinal motility in a model of post-inflammatory accelerated transit: involvement of CB₁ receptors and TRPV1 channels.
Br J Pharmacol. 2014 Sep; 171(17):4026-37.BJ

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+Show Affiliations

Department of Pharmacy, University of Naples Federico II, Naples, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24818658

Citation

Capasso, Raffaele, et al. "Palmitoylethanolamide Normalizes Intestinal Motility in a Model of Post-inflammatory Accelerated Transit: Involvement of CB₁ Receptors and TRPV1 Channels." British Journal of Pharmacology, vol. 171, no. 17, 2014, pp. 4026-37.
Capasso R, Orlando P, Pagano E, et al. Palmitoylethanolamide normalizes intestinal motility in a model of post-inflammatory accelerated transit: involvement of CB₁ receptors and TRPV1 channels. Br J Pharmacol. 2014;171(17):4026-37.
Capasso, R., Orlando, P., Pagano, E., Aveta, T., Buono, L., Borrelli, F., Di Marzo, V., & Izzo, A. A. (2014). Palmitoylethanolamide normalizes intestinal motility in a model of post-inflammatory accelerated transit: involvement of CB₁ receptors and TRPV1 channels. British Journal of Pharmacology, 171(17), 4026-37. https://doi.org/10.1111/bph.12759
Capasso R, et al. Palmitoylethanolamide Normalizes Intestinal Motility in a Model of Post-inflammatory Accelerated Transit: Involvement of CB₁ Receptors and TRPV1 Channels. Br J Pharmacol. 2014;171(17):4026-37. PubMed PMID: 24818658.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Palmitoylethanolamide normalizes intestinal motility in a model of post-inflammatory accelerated transit: involvement of CB₁ receptors and TRPV1 channels. AU - Capasso,Raffaele, AU - Orlando,Pierangelo, AU - Pagano,Ester, AU - Aveta,Teresa, AU - Buono,Lorena, AU - Borrelli,Francesca, AU - Di Marzo,Vincenzo, AU - Izzo,Angelo A, PY - 2014/03/14/received PY - 2014/04/15/revised PY - 2014/04/23/accepted PY - 2014/5/14/entrez PY - 2014/5/14/pubmed PY - 2015/5/12/medline SP - 4026 EP - 37 JF - British journal of pharmacology JO - Br J Pharmacol VL - 171 IS - 17 N2 - 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. SN - 1476-5381 UR - https://www.unboundmedicine.com/medline/citation/24818658/Palmitoylethanolamide_normalizes_intestinal_motility_in_a_model_of_post_inflammatory_accelerated_transit:_involvement_of_CB₁_receptors_and_TRPV1_channels_ L2 - https://doi.org/10.1111/bph.12759 DB - PRIME DP - Unbound Medicine ER -