Multiple actions of anandamide on neonatal rat cultured sensory neurones

R. M. Evans, Roderick Hamilton Scott, Ruth Alexandra Ross

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Abstract

1 We have investigated the effects of the endocannabinoid anandamide ( AEA) on neuronal excitability and vanilloid TRPV1 receptors in neonatal rat cultured dorsal root ganglion neurones.

2 Using whole-cell patch-clamp electrophysiology, we found that AEA inhibits high-voltage-activated Ca2+ currents by 33+/-9% (five out of eight neurones) in the absence of the CB1 receptor antagonist SR141716A (100 nM) and by 32+/-6% (seven out of 10 neurones) in the presence of SR141716A.

3 Fura-2 fluorescence Ca2+ imaging revealed that AEA produced distinct effects on Ca2+ transients produced by depolarisation evoked by 30 mM KCl. In a population of neurones of larger somal area (372+/-20 mum(2)), it significantly enhanced Ca2+ transients (80.26+/-13.12% at 1 muM), an effect that persists after pertussis toxin pretreatment. In a population of neurones of smaller somal area (279+/-18 mum(2)), AEA significantly inhibits Ca2+ transients (30.75+/-3.54% at 1 muM), an effect that is abolished by PTX pretreatment.

4 Extracellular application of 100 nM AEA failed to evoke TRPV1 receptor inward currents in seven out of eight neurones that responded to capsaicin (1 muM), with a mean inward current of -0.94+/-0.21 nA. In contrast, intracellular application of 100 nM AEA elicited robust inward currents in similar to62% of neurones, the mean population response was -0.85+/-0.21 nA. When AEA was applied to the intracellular environment with capsazepine (1 muM), the mean population inward current was -0.01+/-0.01 nA. Under control conditions, mean population current fluctuations of -0.09+/-0.05 nA were observed.

Original languageEnglish
Pages (from-to)1223-1233
Number of pages10
JournalBritish Journal of Pharmacology
Volume141
Issue number7
DOIs
Publication statusPublished - Apr 2004

Keywords

  • cannabinoid
  • anandamide
  • vanilloid
  • TRPV1
  • calcium channels
  • capsaicin
  • SR141716A
  • dorsal root ganglion
  • pain
  • ROOT GANGLION NEURONS
  • CALCIUM-CHANNEL CURRENTS
  • VANILLOID VR1 RECEPTORS
  • IN-SITU HYBRIDIZATION
  • CANNABINOID RECEPTOR
  • CB1 RECEPTOR
  • CAPSAICIN RECEPTORS
  • CAMP ACCUMULATION
  • MOUSE-BRAIN
  • WIN 55212-2

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