title: Cannabinoid 1 receptor activation inhibits transient receptor potential vanilloid type 1 receptor-mediated cationic influx into rat cultured primary sensory neurons.
abstract: The majority of polymodal nociceptors express the non-selective cationic channel, transient receptor potential vanilloid type 1 receptor, which plays a pivotal role in the development of inflammatory heat hyperalgesia and visceral hyper-reflexia. Thus, blocking transient receptor potential vanilloid type 1 receptor-mediated signalling in primary sensory neurons would provide significant pain relief and reduced visceral hyperactivity in inflammatory conditions. Here, we report that cannabinoids including the endogenous agent, anandamide (3-30 nM) and the synthetic compounds, arachidonyl-2-chloroethylamide (500 nM) and 1,1-dimethylheptyl-11-hydroxytetrahydrocannabinol (1 microM) significantly reduce cobalt influx that is mediated through the transient receptor potential vanilloid type 1 receptor in rat cultured primary sensory neurons. The cannabinoid-evoked inhibitory effect can be reversed by rimonabant (200 nM), an antagonist of the cannabinoid 1 receptor. While anandamide- and arachidonyl-2-chloroethylamide fail to evoke inhibitory effects on the transient receptor potential vanilloid type 1 receptor-mediated responses, the inhibitory effect of 1,1-dimethylheptyl-11-hydroxytetrahydrocannabinol is maintained, when the cannabinoids are applied together with the inflammatory mediators, prostaglandin E(2) (10 microM) and bradykinin (10 microM). These results indicate that activation of the cannabinoid 1 receptor can reduce the activity of the transient receptor potential vanilloid type 1 receptor in primary sensory neurons, though the inhibitory effect of agents, which activate both the cannabinoid 1 and the transient receptor potential vanilloid type 1 receptor could be reduced in inflammatory conditions.
authors.affiliation: Department of Anaesthetics, Pain Medicine and Intensive Care, Faculty of Medicine, Imperial College London, Chelsea and Westminster Hospital, 369 Fulham Road, London SW10 9NH, UK.
authors.forename: A
authors.initials: A
authors.lastname: Mahmud
authors.forename: P
authors.initials: P
authors.lastname: Santha
authors.forename: C C
authors.initials: CC
authors.lastname: Paule
authors.forename: I
authors.initials: I
authors.lastname: Nagy
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D002413:Cations, Divalent; D002478:Cells, Cultured; D003035:Cobalt / Q000378:metabolism*; D015232:Dinoprostone / Q000494:pharmacology; D013759:Dronabinol / Q000031:analogs & derivatives / Q000494:pharmacology; D063388:Endocannabinoids; D005260:Female; D053284:Polyunsaturated Alkamides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists*; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000378:metabolism*; D050916:TRPV Cation Channels / Q000502:physiology*
chemical_list: D001095:Arachidonic Acids; D002413:Cations, Divalent; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; D043884:Receptor, Cannabinoid, CB1; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; C119325:arachidonyl-2-chloroethylamide; D003035:Cobalt; D013759:Dronabinol; D015232:Dinoprostone; C062018:HU 211; D002211:Capsaicin; D001920:Bradykinin; C078814:anandamide