{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:16:36Z","timestamp":1787015796170,"version":"build-2736575974"},"reference-count":35,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2017,7,11]],"date-time":"2017-07-11T00:00:00Z","timestamp":1499731200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["DFG; SI 1477\/1\u20101"],"award-info":[{"award-number":["DFG; SI 1477\/1\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2017,12]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n \n Endocannabinoid anandamide (\n AEA<\/jats:styled-content>\n ) inhibits intestinal motility and visceral pain, but it may also be proalgesic through transient receptor potential vanilloid\u20101 (\n TRPV<\/jats:styled-content>\n 1).\n AEA<\/jats:styled-content>\n is degraded by fatty acid amide hydrolase (\n FAAH<\/jats:styled-content>\n ). This study explored whether dual inhibition of\n FAAH<\/jats:styled-content>\n and\n TRPV<\/jats:styled-content>\n 1 reduces diarrhea and abdominal pain.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Immunostaining was performed on myenteric plexus of the mouse colon. The effects of the dual\n FAAH<\/jats:styled-content>\n \/\n TRPV<\/jats:styled-content>\n 1 inhibitor\n AA<\/jats:styled-content>\n \u20105\u2010\n HT<\/jats:styled-content>\n on electrically induced contractility, excitatory junction potential (\n EJP<\/jats:styled-content>\n ) and fast (f) and slow (s) inhibitory junction potentials (\n IJP<\/jats:styled-content>\n ) in the mouse colon\n ,<\/jats:italic>\n colonic propulsion and visceromotor response (\n VMR<\/jats:styled-content>\n ) to rectal distension were studied. The colonic levels of endocannabinoids and fatty acid amides were measured.\n <\/jats:p>\n <\/jats:sec>\n \n Key Results<\/jats:title>\n \n CB<\/jats:styled-content>\n 1\u2010positive neurons exhibited\n TRPV<\/jats:styled-content>\n 1; only some\n TRPV<\/jats:styled-content>\n 1 positive neurons did not express\n CB<\/jats:styled-content>\n 1.\n CB<\/jats:styled-content>\n 1 and\n FAAH<\/jats:styled-content>\n did not colocalize.\n AA<\/jats:styled-content>\n \u20105\u2010\n HT<\/jats:styled-content>\n (100\u00a0\n nM<\/jats:styled-content>\n \u201010\u00a0\u03bcM) decreased colonic contractility by ~60%; this effect was abolished by\n TRPV<\/jats:styled-content>\n 1 antagonist 5\u2032\u2010\n IRTX<\/jats:styled-content>\n , but not by\n CB<\/jats:styled-content>\n 1 antagonist,\n SR<\/jats:styled-content>\n 141716.\n AA<\/jats:styled-content>\n \u20105\u2010\n HT<\/jats:styled-content>\n (1\u00a0\u03bcM\u201010\u00a0\u03bcM) inhibited\n EJP<\/jats:styled-content>\n by ~30% and\n IJP<\/jats:styled-content>\n s by ~50%. The effects of\n AA<\/jats:styled-content>\n \u20105\u2010\n HT<\/jats:styled-content>\n on junction potentials were reversed by\n SR<\/jats:styled-content>\n 141716 and 5`\u2010\n IRTX<\/jats:styled-content>\n .\n AA<\/jats:styled-content>\n \u20105\u2010\n HT<\/jats:styled-content>\n (20\u00a0mg\/kg; i.p.) inhibited colonic propulsion by ~30%;\n SR<\/jats:styled-content>\n 141716 but not 5`\u2010\n IRTX<\/jats:styled-content>\n reversed this effect.\n AA<\/jats:styled-content>\n \u20105\u2010\n HT<\/jats:styled-content>\n decreased\n VMR<\/jats:styled-content>\n by ~50%\u201060%; these effects were not blocked by\n SR<\/jats:styled-content>\n 141716 or 5`\u2010\n IRTX<\/jats:styled-content>\n .\n AA<\/jats:styled-content>\n \u20105\u2010\n HT<\/jats:styled-content>\n increased\n AEA<\/jats:styled-content>\n in the colon.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Inferences<\/jats:title>\n \n The effects of\n AA<\/jats:styled-content>\n \u20105\u2010\n HT<\/jats:styled-content>\n on visceral sensation and colonic motility are differentially mediated by\n CB<\/jats:styled-content>\n 1,\n TRPV<\/jats:styled-content>\n 1 and non\u2010\n CB<\/jats:styled-content>\n 1\/\n TRPV<\/jats:styled-content>\n 1 mechanisms, possibly reflecting the distinct neuromodulatory roles of endocannabinoid and endovanilloid\n FAAH<\/jats:styled-content>\n substrates in the mouse intestine.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/nmo.13148","type":"journal-article","created":{"date-parts":[[2017,7,11]],"date-time":"2017-07-11T01:56:42Z","timestamp":1499738202000},"source":"Crossref","is-referenced-by-count":14,"title":["Targeting fatty acid amide hydrolase and transient receptor potential vanilloid\u20101 simultaneously to modulate colonic motility and visceral sensation in the mouse: A pharmacological intervention with N\u2010arachidonoyl\u2010serotonin (\n AA<\/scp>\n \u20105\u2010\n HT<\/scp>\n )"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3237-4715","authenticated-orcid":false,"given":"M.","family":"Bashashati","sequence":"first","affiliation":[{"name":"Snyder Institute for Chronic Diseases University of Calgary Calgary AB Canada"},{"name":"Division of Gastroenterology Department of Internal Medicine Texas Tech University Health Sciences Center\/Paul L. 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