Oleoylethanolamine and palmitoylethanolamine modulate intestinal permeability in vitro via TRPV1 and PPARα
Cannabinoids modulate intestinal permeability through cannabinoid receptor 1 (CB1). The endocannabinoid-like compounds oleoylethanolamine (OEA) and palmitoylethanolamine (PEA) play an important role in digestive regulation, and we hypothesized they would also modulate intestinal permeability. Transe...
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| Format: | Article |
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Federation of American Society of Experimental Biology
2016
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| Online Access: | https://eprints.nottingham.ac.uk/45051/ |
| _version_ | 1848797058200240128 |
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| author | Karwad, Mustafa A. Macpherson, Tara Wang, Bo Theophilidou, Elena Sarmad, Sarir Barrett, David A. Larvin, Michael Wright, Karen L. Lund, Jonathan N. O'Sullivan, Saoirse |
| author_facet | Karwad, Mustafa A. Macpherson, Tara Wang, Bo Theophilidou, Elena Sarmad, Sarir Barrett, David A. Larvin, Michael Wright, Karen L. Lund, Jonathan N. O'Sullivan, Saoirse |
| author_sort | Karwad, Mustafa A. |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | Cannabinoids modulate intestinal permeability through cannabinoid receptor 1 (CB1). The endocannabinoid-like compounds oleoylethanolamine (OEA) and palmitoylethanolamine (PEA) play an important role in digestive regulation, and we hypothesized they would also modulate intestinal permeability. Transepithelial electrical resistance (TEER) was measured in human Caco-2 cells to assess permeability after application of OEA and PEA and relevant antagonists. Cells treated with OEA and PEA were stained for cytoskeletal F-actin changes and lysed for immunoassay. OEA and PEA were measured by liquid chromatography–tandem mass spectrometry. OEA (applied apically, logEC50 −5.4) and PEA (basolaterally, logEC50 −4.9; apically logEC50 −5.3) increased Caco-2 resistance by 20–30% via transient receptor potential vanilloid (TRPV)-1 and peroxisome proliferator-activated receptor (PPAR)-α. Preventing their degradation (by inhibiting fatty acid amide hydrolase) enhanced the effects of OEA and PEA. OEA and PEA induced cytoskeletal changes and activated focal adhesion kinase and ERKs 1/2, and decreased Src kinases and aquaporins 3 and 4. In Caco-2 cells treated with IFNγ and TNFα, OEA (via TRPV1) and PEA (via PPARα) prevented or reversed the cytokine-induced increased permeability compared to vehicle (0.1% ethanol). PEA (basolateral) also reversed increased permeability when added 48 or 72 h after cytokines (P < 0.001, via PPARα). Cellular and secreted levels of OEA and PEA (P < 0.001–0.001) were increased in response to inflammatory mediators. OEA and PEA have endogenous roles and potential therapeutic applications in conditions of intestinal hyperpermeability and inflammation. |
| first_indexed | 2025-11-14T19:57:50Z |
| format | Article |
| id | nottingham-45051 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:57:50Z |
| publishDate | 2016 |
| publisher | Federation of American Society of Experimental Biology |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-450512020-05-04T18:12:38Z https://eprints.nottingham.ac.uk/45051/ Oleoylethanolamine and palmitoylethanolamine modulate intestinal permeability in vitro via TRPV1 and PPARα Karwad, Mustafa A. Macpherson, Tara Wang, Bo Theophilidou, Elena Sarmad, Sarir Barrett, David A. Larvin, Michael Wright, Karen L. Lund, Jonathan N. O'Sullivan, Saoirse Cannabinoids modulate intestinal permeability through cannabinoid receptor 1 (CB1). The endocannabinoid-like compounds oleoylethanolamine (OEA) and palmitoylethanolamine (PEA) play an important role in digestive regulation, and we hypothesized they would also modulate intestinal permeability. Transepithelial electrical resistance (TEER) was measured in human Caco-2 cells to assess permeability after application of OEA and PEA and relevant antagonists. Cells treated with OEA and PEA were stained for cytoskeletal F-actin changes and lysed for immunoassay. OEA and PEA were measured by liquid chromatography–tandem mass spectrometry. OEA (applied apically, logEC50 −5.4) and PEA (basolaterally, logEC50 −4.9; apically logEC50 −5.3) increased Caco-2 resistance by 20–30% via transient receptor potential vanilloid (TRPV)-1 and peroxisome proliferator-activated receptor (PPAR)-α. Preventing their degradation (by inhibiting fatty acid amide hydrolase) enhanced the effects of OEA and PEA. OEA and PEA induced cytoskeletal changes and activated focal adhesion kinase and ERKs 1/2, and decreased Src kinases and aquaporins 3 and 4. In Caco-2 cells treated with IFNγ and TNFα, OEA (via TRPV1) and PEA (via PPARα) prevented or reversed the cytokine-induced increased permeability compared to vehicle (0.1% ethanol). PEA (basolateral) also reversed increased permeability when added 48 or 72 h after cytokines (P < 0.001, via PPARα). Cellular and secreted levels of OEA and PEA (P < 0.001–0.001) were increased in response to inflammatory mediators. OEA and PEA have endogenous roles and potential therapeutic applications in conditions of intestinal hyperpermeability and inflammation. Federation of American Society of Experimental Biology 2016-09-13 Article PeerReviewed Karwad, Mustafa A., Macpherson, Tara, Wang, Bo, Theophilidou, Elena, Sarmad, Sarir, Barrett, David A., Larvin, Michael, Wright, Karen L., Lund, Jonathan N. and O'Sullivan, Saoirse (2016) Oleoylethanolamine and palmitoylethanolamine modulate intestinal permeability in vitro via TRPV1 and PPARα. FASEB Journal, 31 (2). pp. 469-481. ISSN 1530-6860 gut cannibinoid nuclear receptor http://www.fasebj.org/content/31/2/469 doi:10.1096/fj.201500132 doi:10.1096/fj.201500132 |
| spellingShingle | gut cannibinoid nuclear receptor Karwad, Mustafa A. Macpherson, Tara Wang, Bo Theophilidou, Elena Sarmad, Sarir Barrett, David A. Larvin, Michael Wright, Karen L. Lund, Jonathan N. O'Sullivan, Saoirse Oleoylethanolamine and palmitoylethanolamine modulate intestinal permeability in vitro via TRPV1 and PPARα |
| title | Oleoylethanolamine and palmitoylethanolamine modulate intestinal permeability in vitro via TRPV1 and PPARα |
| title_full | Oleoylethanolamine and palmitoylethanolamine modulate intestinal permeability in vitro via TRPV1 and PPARα |
| title_fullStr | Oleoylethanolamine and palmitoylethanolamine modulate intestinal permeability in vitro via TRPV1 and PPARα |
| title_full_unstemmed | Oleoylethanolamine and palmitoylethanolamine modulate intestinal permeability in vitro via TRPV1 and PPARα |
| title_short | Oleoylethanolamine and palmitoylethanolamine modulate intestinal permeability in vitro via TRPV1 and PPARα |
| title_sort | oleoylethanolamine and palmitoylethanolamine modulate intestinal permeability in vitro via trpv1 and pparα |
| topic | gut cannibinoid nuclear receptor |
| url | https://eprints.nottingham.ac.uk/45051/ https://eprints.nottingham.ac.uk/45051/ https://eprints.nottingham.ac.uk/45051/ |