{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T15:39:58Z","timestamp":1759333198553,"version":"3.40.5"},"reference-count":55,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,11,27]],"date-time":"2019-11-27T00:00:00Z","timestamp":1574812800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1159744"],"award-info":[{"award-number":["APP1159744"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>The fine control of food intake is important for the maintenance of a healthy metabolic state.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Gastric vagal afferents (GVAs) are involved in the peripheral regulation of food intake via signalling the degree of distension of the stomach which ultimately leads to feelings of fullness and satiety.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>This study provides evidence that endocannabinoids such as anandamide are capable of regulating GVA sensitivity in a concentration\u2010dependent biphasic manner.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>This biphasic effect is dependent upon interactions between the CB1, TRPV1 and GHSR receptors.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These data have important implications for the peripheral control of food intake.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Gastric vagal afferents (GVAs) signal to the hindbrain resulting in satiety. Endocannabinoids are endogenous ligands of cannabinoid 1 receptor (CB1) and transient receptor potential vanilloid\u20101 (TRPV1) channels. The endocannabinoid anandamide (AEA) is expressed in the stomach, and its receptor CB1 is expressed in ghrelin\u2010positive gastric mucosal cells. Further, TRPV1, CB1 and growth hormone secretagogue receptor (ghrelin receptor, GHSR) are expressed in subpopulations of GVA neurons. This study aimed to determine the interaction between TRPV1, CB1, GHSR and endocannabinoids in the modulation of GVA signalling. An <jats:italic>in vitro<\/jats:italic> electrophysiology preparation was used to assess GVA mechanosensitivity in male C57BL\/6 mice. Effects of methanandamide (mAEA; 1\u2013100\u00a0n<jats:sc>m<\/jats:sc>), on GVA responses to stretch were determined in the absence and presence of antagonists of CB1, TRPV1, GHSR, protein kinase\u2010A (PKA), protein kinase\u2010C (PKC) and G\u2010protein subunits G\u03b1<jats:sub>i\/o<\/jats:sub>, or G\u03b1<jats:sub>q<\/jats:sub>. Low doses (1\u201310\u00a0n<jats:sc>m<\/jats:sc>) of mAEA reduced GVA responses to 3\u00a0g stretch, whereas high doses (30\u2013100\u00a0n<jats:sc>m<\/jats:sc>) increased the response. The inhibitory and excitatory effects of mAEA (1\u2013100\u00a0n<jats:sc>m<\/jats:sc>) were reduced\/lost in the presence of a CB1 and TRPV1 antagonist. PKA, G\u03b1<jats:sub>i\/o<\/jats:sub> or GHSR antagonists prevented the inhibitory effect of mAEA on GVA mechanosensitivity. Conversely, in the presence of a PKC or G\u03b1<jats:sub>q<\/jats:sub> antagonist the excitatory effect of mAEA was reduced or lost, respectively. Activation of CB1, by mAEA, can activate or inhibit TRPV1 to increase or decrease GVA responses to stretch, depending on the pathway activated. These interactions could play an important role in the fine control of food intake.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp278696","type":"journal-article","created":{"date-parts":[[2019,10,23]],"date-time":"2019-10-23T10:47:52Z","timestamp":1571827672000},"page":"139-150","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Biphasic effects of methanandamide on murine gastric vagal afferent mechanosensitivity"],"prefix":"10.1113","volume":"598","author":[{"given":"Stewart","family":"Christie","sequence":"first","affiliation":[{"name":"Vagal Afferent Research Group Centre for Nutrition and Gastrointestinal Disease Adelaide Medical School University of Adelaide  Adelaide SA 5005 Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca","family":"O'Rielly","sequence":"additional","affiliation":[{"name":"Vagal Afferent Research Group Centre for Nutrition and Gastrointestinal Disease Adelaide Medical School University of Adelaide  Adelaide SA 5005 Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Li","sequence":"additional","affiliation":[{"name":"Vagal Afferent Research Group Centre for Nutrition and Gastrointestinal Disease Adelaide Medical School University of Adelaide  Adelaide SA 5005 Australia"},{"name":"Lifelong Health South Australian Health and Medical Research Institute  Adelaide SA 5000 Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary A.","family":"Wittert","sequence":"additional","affiliation":[{"name":"Vagal Afferent Research Group Centre for Nutrition and Gastrointestinal Disease Adelaide Medical School University of Adelaide  Adelaide SA 5005 Australia"},{"name":"Lifelong Health South Australian Health and Medical Research Institute  Adelaide SA 5000 Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7086-5865","authenticated-orcid":false,"given":"Amanda J.","family":"Page","sequence":"additional","affiliation":[{"name":"Vagal Afferent Research Group Centre for Nutrition and Gastrointestinal Disease Adelaide Medical School University of Adelaide  Adelaide SA 5005 Australia"},{"name":"Lifelong Health South Australian Health and Medical Research Institute  Adelaide SA 5000 Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,11,27]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14052"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2016.12.044"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2013.08.047"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.1983.245.3.G334"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.020750"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.regpep.2007.08.024"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2032100100"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2014.11.006"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00543.2005"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2003-031267"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12823"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2826.2008.01686.x"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2010.00908.x"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/WNR.0b013e32832a0a5f"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2001.00406.x"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.428144"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.581397"},{"key":"e_1_2_5_19_1","first-page":"602","article-title":"Suramin analogues as subtype\u2010selective G protein inhibitors","volume":"49","author":"Freissmuth M","year":"1996","journal-title":"Mol Pharmacol"},{"key":"e_1_2_5_20_1","doi-asserted-by":"crossref","first-page":"14579","DOI":"10.1016\/S0021-9258(18)71718-3","article-title":"Protein kinase inhibitor\u2010(6\u201022)\u2010amide peptide analogs with standard and nonstandard amino acid substitutions for phenylalanine 10. 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