Endocannabinoids, anandamide and 2-AG, regulate mechanosensitivity of mucosal afferents in the Guinea pig bladder

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dc.contributor.authorRamsay, S.
dc.contributor.authorSpencer, N.J.
dc.contributor.authorZagorodnyuk, V.
dc.date.issued2023
dc.description.abstractBladder afferents play a crucial role in urine storage and voiding, and conscious sensations from the bladder. Endocannabinoids, anandamide (AEA) and 2-arachidonolylglycerol (2-AG), are endogenous ligands of G-protein coupled cannabinoid receptors 1 and 2 (CB1 and CB2) found in the CNS and peripheral organs. They also have off-target effects on some ligand- and voltage-gated channels. The aim of this study is to determine the role of AEA and 2-AG in regulation of mechanosensitivity of probable nociceptive neurons innervating the bladder - capsaicin-sensitive mucosal afferents. The activity of these afferents was determined by ex vivo single unit extracellular recordings in the guinea pig bladder. A stable analogue of anandamide, methanandamide (mAEA) evoked initial excitatory response of mucosal afferents followed by potentiation of their responses to mechanical stimulation. In the presence of TRPV1 antagonist (AMG9810), mAEA’s effect on mechanosensitivity switched from excitatory to inhibitory. The inhibitory effect of mAEA is due to activation of both CB1 and CB2 cannabinoid receptors since it was abolished by combined application of selective CB1 (NESS0327) and CB2 (SR144528) antagonists. 2-AG application evoked a brief excitation of mucosal afferents, without potentiation of their mechanosensitivity, followed by the inhibition of their responses to mechanical stimulation. CB2 receptor antagonist, SR144528 abolished the inhibitory effect of 2-AG. Our data indicated that anandamide and 2-AG have opposite effects on mechanosensitivity of mucosal capsaicin-sensitive afferents in the guinea pig bladder; mAEA potentiated while 2-AG inhibited responses of mucosal afferents to mechanical stimulation. These findings are important for understanding of the role of endocannabinoids in regulating bladder sensation and function.
dc.description.statementofresponsibilityStewart Ramsay , Nick J. Spencer, Vladimir Zagorodnyuk
dc.identifier.citationEuropean Journal of Pharmacology, 2023; 945:175624-1-175624-9
dc.identifier.doi10.1016/j.ejphar.2023.175624
dc.identifier.issn0014-2999
dc.identifier.issn1879-0712
dc.identifier.orcidRamsay, S. [0000-0003-2068-3868]
dc.identifier.urihttps://hdl.handle.net/2440/138059
dc.language.isoen
dc.publisherElsevier BV
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1184546
dc.rights© 2023 Elsevier B.V. All rights reserved.
dc.source.urihttps://doi.org/10.1016/j.ejphar.2023.175624
dc.subjectEndocannabinoids; Anandamide; 2-AG; CB1 and CB2 cannabinoid receptors; Bladder afferents
dc.subject.meshAnimals
dc.subject.meshGuinea Pigs
dc.subject.meshCapsaicin
dc.subject.meshReceptors, Cannabinoid
dc.subject.meshReceptor, Cannabinoid, CB1
dc.subject.meshReceptor, Cannabinoid, CB2
dc.subject.meshEndocannabinoids
dc.subject.meshUrinary Bladder
dc.subject.meshPolyunsaturated Alkamides
dc.titleEndocannabinoids, anandamide and 2-AG, regulate mechanosensitivity of mucosal afferents in the Guinea pig bladder
dc.typeJournal article
pubs.publication-statusPublished

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