BACKGROUND AND PURPOSE: Palmitoylethanolamide (PEA) acts via several targets, including cannabinoid CB1 and CB2 receptors, transient receptor potential vanilloid type-1 (TRPV1) ion channels, peroxisome proliferator-activated receptor alpha (PPAR α) and orphan G protein-coupled receptor 55 (GRR55), all involved in the control of intestinal inflammation. Here, we investigated the effect of PEA in a murine model of colitis. EXPERIMENTAL APPROACH: Colitis was induced in mice by intracolonic administration of dinitrobenzenesulfonic acid (DNBS). Inflammation was assessed by evaluating inflammatory markers/parameters and by histology; intestinal permeability by a fluorescent method; colonic cell proliferation by immunohistochemistry; PEA and endocannabinoid levels by liquid chromatography mass spectrometry; receptor and enzyme mRNA expression by quantitative RT-PCR. KEY RESULTS: DNBS administration caused inflammatory damage, increased colonic levels of PEA and endocannabinoids, down-regulation of mRNA for TRPV1 and GPR55 but no changes in mRNA for CB1 , CB2 and PPARα. Exogenous PEA (i.p. and/or p.o., 1 mg·kg(-1) ) attenuated inflammation and intestinal permeability, stimulated colonic cell proliferation, and increased colonic TRPV1 and CB1 receptor expression. The anti-inflammatory effect of PEA was attenuated or abolished by CB2 receptor, GPR55 or PPARα antagonists and further increased by the TRPV1 antagonist capsazepine. CONCLUSIONS AND IMPLICATIONS: PEA improves murine experimental colitis, the effect being mediated by CB2 receptors, GPR55 and PPARα, and modulated by TRPV1 channels.
BACKGROUND AND PURPOSE:Palmitoylethanolamide (PEA) acts via several targets, including cannabinoid CB1 and CB2 receptors, transient receptor potential vanilloid type-1 (TRPV1) ion channels, peroxisome proliferator-activated receptor alpha (PPAR α) and orphan G protein-coupled receptor 55 (GRR55), all involved in the control of intestinal inflammation. Here, we investigated the effect of PEA in a murine model of colitis. EXPERIMENTAL APPROACH: Colitis was induced in mice by intracolonic administration of dinitrobenzenesulfonic acid (DNBS). Inflammation was assessed by evaluating inflammatory markers/parameters and by histology; intestinal permeability by a fluorescent method; colonic cell proliferation by immunohistochemistry; PEA and endocannabinoid levels by liquid chromatography mass spectrometry; receptor and enzyme mRNA expression by quantitative RT-PCR. KEY RESULTS:DNBS administration caused inflammatory damage, increased colonic levels of PEA and endocannabinoids, down-regulation of mRNA for TRPV1 and GPR55 but no changes in mRNA for CB1 , CB2 and PPARα. Exogenous PEA (i.p. and/or p.o., 1 mg·kg(-1) ) attenuated inflammation and intestinal permeability, stimulated colonic cell proliferation, and increased colonic TRPV1 and CB1 receptor expression. The anti-inflammatory effect of PEA was attenuated or abolished by CB2 receptor, GPR55 or PPARα antagonists and further increased by the TRPV1 antagonist capsazepine. CONCLUSIONS AND IMPLICATIONS: PEA improves murine experimental colitis, the effect being mediated by CB2 receptors, GPR55 and PPARα, and modulated by TRPV1 channels.
Authors: András Dömötör; Zsanett Peidl; Aron Vincze; Béla Hunyady; János Szolcsányi; László Kereskay; György Szekeres; Gyula Mózsik Journal: Inflammopharmacology Date: 2005 Impact factor: 4.473
Authors: Jin Fu; Giuseppe Astarita; Silvana Gaetani; Janet Kim; Benjamin F Cravatt; Ken Mackie; Daniele Piomelli Journal: J Biol Chem Date: 2006-11-22 Impact factor: 5.157
Authors: B Romano; F Borrelli; I Fasolino; R Capasso; F Piscitelli; Mg Cascio; Rg Pertwee; D Coppola; L Vassallo; P Orlando; V Di Marzo; Aa Izzo Journal: Br J Pharmacol Date: 2013-05 Impact factor: 8.739
Authors: Stephen P H Alexander; Helen E Benson; Elena Faccenda; Adam J Pawson; Joanna L Sharman; Michael Spedding; John A Peters; Anthony J Harmar Journal: Br J Pharmacol Date: 2013-12 Impact factor: 8.739
Authors: Stephen P H Alexander; Helen E Benson; Elena Faccenda; Adam J Pawson; Joanna L Sharman; William A Catterall; Michael Spedding; John A Peters; Anthony J Harmar Journal: Br J Pharmacol Date: 2013-12 Impact factor: 8.739
Authors: Angelo A Izzo; Mauro Teixeira; Steve P H Alexander; Giuseppe Cirino; James R Docherty; Christopher H George; Paul A Insel; Yong Ji; David A Kendall; Reynold A Panattieri; Christopher G Sobey; S Clare Stanford; Barbara Stefanska; Gary Stephens; Amrita Ahluwalia Journal: Br J Pharmacol Date: 2020-04-16 Impact factor: 8.739
Authors: A Stančić; K Jandl; C Hasenöhrl; F Reichmann; G Marsche; R Schuligoi; A Heinemann; M Storr; R Schicho Journal: Neurogastroenterol Motil Date: 2015-07-30 Impact factor: 3.598