Actions of cannabinoid receptor ligands on rat cultured sensory neurones: implications for antinociception

Ruth Alexandra Ross, Angela Alice Coutts, Shona Moira McFarlane, Sharon Anavi-Goffer, A. J. Irving, Roger Guy Pertwee, David Joseph MacEwan, Roderick Hamilton Scott

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148 Citations (Scopus)

Abstract

Cannabinoids modulate nociceptive processing in models of acute, inflammatory and neuropathic pain. We have investigated the location and function of cannabinoid receptors on cultured neonatal dorsal root ganglion (DRG) neurones and F-11 cells, a dorsal root ganglionxneuroblastoma hybridoma which displays several of the features of authentic DRG neurones. CB1 receptor immunolabelling was observed on the cell bodies and as fine puncta on processes of both cultured DRG neurones and F-11 cells. Additionally, fluorescence-activated cell sorting (FACS) analysis provided evidence that both CB1 and CB2 receptors are expressed on populations of cells within the cultured DRG and F-11 cells. The cannabinoid receptor agonist (+)-WIN55212 (10 and 100 nM) inhibited the mean voltage-activated Ca2+ current in DRG neurones by 21% and 30%, respectively. The isomer, (-)-WIN55212 (10 and 100 nM) produced significantly less inhibition of 6% and 10% respectively. The CB1 selective receptor antagonist SR141716A (100 nM) enhanced the peak high voltage-activated Ca2+ current by 24% and simultaneous application of SR141716A (100 nM) and (+)-WIN55212 (100 nM) resulted in a significant attenuation of the inhibition obtained with (+)-WIN55212 alone. These data give functional evidence for the hypothesis that the analgesic actions of cannabinoids may be mediated by presynaptic inhibition of transmitter release in sensory neurones. (C) 2000 Elsevier Science Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)221-232
Number of pages11
JournalNeuropharmacology
Volume40
Issue number2
Early online date12 Dec 2000
DOIs
Publication statusPublished - Jan 2001

Keywords

  • cannabinoid receptors
  • DRG
  • F-11
  • calcium channels
  • inverse agonism
  • DORSAL-ROOT GANGLIA
  • INHIBIT N-TYPE
  • CALCIUM CHANNELS
  • CB1 RECEPTORS
  • NEUROBLASTOMA-CELLS
  • HIPPOCAMPAL-NEURONS
  • INVERSE AGONIST
  • BRAIN MEMBRANES
  • ANANDAMIDE
  • PAIN

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