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  • Title: Cannabinoid 1 receptor activation inhibits transient receptor potential vanilloid type 1 receptor-mediated cationic influx into rat cultured primary sensory neurons.
    Author: Mahmud A, Santha P, Paule CC, Nagy I.
    Journal: Neuroscience; 2009 Sep 15; 162(4):1202-11. PubMed ID: 19463903.
    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.
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