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The endocannabinoids anandamide and 2-arachidonoylglycerol inhibit cholinergic contractility in the human colon

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dc.contributor.authorSmid, S.
dc.contributor.authorBjorklund, C.
dc.contributor.authorSvensson, K.
dc.contributor.authorHeigis, S.
dc.contributor.authorRevesz, A.
dc.date.issued2007
dc.descriptionCopyright © 2007 Elsevier B.V. All rights reserved.
dc.description.abstractThe effects of the endocannabinoids anandamide and 2-arachidonoylglycerol (2-AG) were determined on cholinergic contractility in strips of human colonic longitudinal muscle and circular muscle in vitro, in the presence of nitric oxide synthase blockade with N-nitro-l-arginine (10(-4) M). Anandamide and 2-AG inhibited longitudinal muscle and circular muscle contractile responses to acetylcholine (10(-9)-10(-4) M) in a concentration-dependent manner. This was unaltered following pretreatment with the cannabinoid CB(1) receptor-selective antagonist AM251 (10(-7) M), however in isolation AM251 elicited a significant rightward shift in the potency of acetylcholine-evoked contraction in both longitudinal muscle and circular muscle preparations. Pretreatment with an inhibitor of anandamide catabolism, arachidonoyl trifluoromethyl ketone (10(-5) M), alone caused a significant decrease in the potency of acetylcholine-evoked contraction in both longitudinal and circular muscle, but had no significant additional effect on the anandamide-induced (10(-5) M) suppression of contraction. Pretreatment with the cannabinoid CB(2) receptor inverse agonist JTE 907 (10(-6) M) neither influenced the potency of acetylcholine-evoked contraction alone nor prevented the potency shift in acetylcholine-evoked contraction in the presence of anandamide (10(-5) M). The findings of the present study indicate that the endocannabinoids anandamide and 2-arachidonoylglycerol suppress colonic cholinergic contractility via a non conventional cannabinoid or non-cannabinoid receptor-mediated pathway. Cholinergic contraction may be tonically modulated by endocannabinoids and/or products of arachidonate metabolism unrelated to endocannabinoid production. The extent of anandamide metabolism is not sufficient to influence the functional effects of its exogenous administration in human colonic tissue in vitro.
dc.description.statementofresponsibilityScott D. Smid, Charlotta K. Bjorklund, Karin M. Svensson, Sofia Heigis and Aron Revesz
dc.description.urihttp://www.elsevier.com/wps/find/journaldescription.cws_home/506087/description#description
dc.identifier.citationEuropean Journal of Pharmacology, 2007; 575(1-3):168-176
dc.identifier.doi10.1016/j.ejphar.2007.07.036
dc.identifier.issn0014-2999
dc.identifier.issn1879-0712
dc.identifier.orcidSmid, S. [0000-0003-4192-7219]
dc.identifier.urihttp://hdl.handle.net/2440/44632
dc.language.isoen
dc.publisherElsevier Science BV
dc.source.urihttps://doi.org/10.1016/j.ejphar.2007.07.036
dc.subjectColon
dc.subjectCholinergic Fibers
dc.subjectHumans
dc.subjectAcetylcholine
dc.subjectArachidonic Acids
dc.subjectGlycerides
dc.subjectNitroarginine
dc.subjectReceptors, Cannabinoid
dc.subjectEnzyme Inhibitors
dc.subjectEndocannabinoids
dc.subjectMuscle Contraction
dc.subjectDose-Response Relationship, Drug
dc.subjectNitric Oxide Synthase
dc.subjectPolyunsaturated Alkamides
dc.subjectCannabinoid Receptor Modulators
dc.titleThe endocannabinoids anandamide and 2-arachidonoylglycerol inhibit cholinergic contractility in the human colon
dc.typeJournal article
pubs.publication-statusPublished

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