Cannabinoid 1 receptor activation inhibits transient receptor potential vanilloid type 1 receptor-mediated cationic influx into rat cultured primary sensory neurons

A. Mahmud, P. Sántha, C. C. Paule, I. Nagy

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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 μM) 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 E2 (10 μM) and bradykinin (10 μM). 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.

Original languageEnglish
Pages (from-to)1202-1211
Number of pages10
JournalNeuroscience
Volume162
Issue number4
DOIs
Publication statusPublished - Sep 15 2009

Fingerprint

Cannabinoid Receptors
Sensory Receptor Cells
Cannabinoids
rimonabant
Cannabinoid Receptor Antagonists
Transient Receptor Potential Channels
Nociceptors
Hyperalgesia
Bradykinin
Cobalt
Dinoprostone
vanilloid receptor subtype 1
Hot Temperature
Pain

Keywords

  • anandamide
  • capsaicin
  • heat hyperalgesia
  • inflammation
  • pain
  • TRPV1

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

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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",
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 μM) 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 E2 (10 μM) and bradykinin (10 μM). 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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AU - Sántha, P.

AU - Paule, C. C.

AU - Nagy, I.

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