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The endocannabinoid\u2010like 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\u20102 cells to assess permeability after application of OEA and PEA and relevant antagonists. Cells treated with OEA and PEA were stained for cytoskeletal F\u2010actin changes and lysed for immunoassay. OEA and PEA were measured by liquid chromatography\u2010tandem mass spectrometry. OEA (applied apically, logEC50 25.4) and PEA (basolaterally, logEC50 24.9; apically logEC50 25.3) increased Caco\u20102 resistance by 20\u201330% via transient receptor potential vanilloid (TRPV)\u20101 and peroxisome proliferator\u2010activated receptor (PPAR)\u2010a. 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\u20102 cells treated with IFNg and TNFa, OEA (via TRPV1) and PEA (via PPAR\u03b1) prevented or reversed the cytokine\u2010induced increased permeability compared to vehicle (0.1% ethanol). PEA (basolateral) also reversed increased permeability when added 48 or 72 h after cytokines (P &lt;0.001, via PPAR\u03b1). Cellular and secreted levels of OEA and PEA (P &lt;0.001\u20130.001) were increased in response to inflammatory mediators. OEA and PEA have endogenous roles and potential therapeutic applications in conditions of intestinal hyperpermeability and inflammation.\u2014Karwad, M. A., Macpherson, T., Wang, B., Theophilidou, E., Sarmad, S., Barrett, D. A., Larvin, M., Wright, K. L., Lund, J. N., O'Sullivan, S. E. Oleoylethanolamine and palmitoylethanolamine modulate intestinal permeability\n                    <jats:italic>in vitro<\/jats:italic>\n                    via TRPV1 and PPAR\u03b1.\n                    <jats:italic>FASEB J<\/jats:italic>\n                    . 31, 469\u2013481(2017).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201500132","type":"journal-article","created":{"date-parts":[[2016,9,13]],"date-time":"2016-09-13T22:09:23Z","timestamp":1473804563000},"page":"469-481","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":77,"title":["Oleoylethanolamine and palmitoylethanolamine modulate intestinal permeability\n                    <i>in vitro<\/i>\n                    via TRPV1 and PPAR\u03b1"],"prefix":"10.1096","volume":"31","author":[{"given":"Mustafa A.","family":"Karwad","sequence":"first","affiliation":[{"name":"School of Medicine Royal Derby Hospital Nottingham United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tara","family":"Macpherson","sequence":"additional","affiliation":[{"name":"Division of Biomedical and Life Sciences, Faculty of Health and Medicine Lancaster University Lancaster United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Biomedical and Life Sciences, Faculty of Health and Medicine Lancaster University Lancaster United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Theophilidou","sequence":"additional","affiliation":[{"name":"School of Medicine Royal Derby Hospital Nottingham United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarir","family":"Sarmad","sequence":"additional","affiliation":[{"name":"Centre for Analytical Bioscience School of Pharmacy University of Nottingham Nottingham United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Barrett","sequence":"additional","affiliation":[{"name":"Centre for Analytical Bioscience School of Pharmacy University of Nottingham Nottingham United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Larvin","sequence":"additional","affiliation":[{"name":"Graduate Entry Medical School University of Limerick Limerick Ireland"},{"name":"Health Research Institute University of Limerick Limerick Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen L.","family":"Wright","sequence":"additional","affiliation":[{"name":"Division of Biomedical and Life Sciences, Faculty of Health and Medicine Lancaster University Lancaster United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan N.","family":"Lund","sequence":"additional","affiliation":[{"name":"School of Medicine Royal Derby Hospital Nottingham United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saoirse E.","family":"O'Sullivan","sequence":"additional","affiliation":[{"name":"School of Medicine Royal Derby Hospital Nottingham United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,9,13]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3109\/00365521.2014.898326"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2009.05.038"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.3945\/jn.110.135657"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2006.060681"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2653"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2011.07.006"},{"key":"e_1_2_11_8_1","first-page":"456","article-title":"Increased intestinal permeability in patients with inflammatory bowel disease","volume":"9","author":"Welcker K.","year":"2004","journal-title":"Eur. 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