Biphasic effects of methanandamide on murine gastric vagal afferent mechanosensitivity

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dc.contributor.authorChristie, S.
dc.contributor.authorO'Reilly, R.
dc.contributor.authorLi, H.
dc.contributor.authorWittert, G.A.
dc.contributor.authorPage, A.J.
dc.date.issued2020
dc.description.abstractGastric vagal afferents (GVAs) signal to the hindbrain resulting in satiety. Endocannabinoids are endogenous ligands of cannabinoid 1 receptor (CB1) and transient receptor potential vanilloid‐1 (TRPV1) channels. The endocannabinoid anandamide (AEA) is expressed in the stomach, and its receptor CB1 is expressed in ghrelin‐positive 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 in vitro electrophysiology preparation was used to assess GVA mechanosensitivity in male C57BL/6 mice. Effects of methanandamide (mAEA; 1–100 nm), on GVA responses to stretch were determined in the absence and presence of antagonists of CB1, TRPV1, GHSR, protein kinase‐A (PKA), protein kinase‐C (PKC) and G‐protein subunits Gαi/o, or Gαq. Low doses (1–10 nm) of mAEA reduced GVA responses to 3 g stretch, whereas high doses (30–100 nm) increased the response. The inhibitory and excitatory effects of mAEA (1–100 nm) were reduced/lost in the presence of a CB1 and TRPV1 antagonist. PKA, Gαi/o or GHSR antagonists prevented the inhibitory effect of mAEA on GVA mechanosensitivity. Conversely, in the presence of a PKC or Gαq 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.
dc.description.statementofresponsibilityStewart Christie, Rebecca O’Rielly, Hui Li, Gary A. Wittert and Amanda J. Page
dc.identifier.citationJournal of Physiology, 2020; 598(1):139-150
dc.identifier.doi10.1113/jp278696
dc.identifier.issn0022-3751
dc.identifier.issn1469-7793
dc.identifier.orcidChristie, S. [0000-0003-2068-3868]
dc.identifier.orcidLi, H. [0000-0002-1010-516X]
dc.identifier.orcidWittert, G.A. [0000-0001-6818-6065]
dc.identifier.orcidPage, A.J. [0000-0002-7086-5865]
dc.identifier.urihttp://hdl.handle.net/2440/122657
dc.language.isoen
dc.publisherWiley
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1159744
dc.rights© 2019 The Authors. The Journal of Physiology © 2019 The Physiological Society
dc.source.urihttps://doi.org/10.1113/jp278696
dc.subjectAnandamide; gastric vagal afferent; TRPV1
dc.titleBiphasic effects of methanandamide on murine gastric vagal afferent mechanosensitivity
dc.typeJournal article
pubs.publication-statusPublished

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