Abstract
Background and purpose: The endogenous cannabinoid anandamide (AEA) acts at cannabinoid (CB1) and vanilloid (TRPV1) receptors. AEA also shows antinociceptive properties; although the underlying mechanism for this is not fully understood, both CB1 and TRPV1 may be involved. Voltage-activated Ca2+ channels in rat-cultured dorsal root ganglion (DRG) neurons are modulated by AEA. However, AEA in different populations of neurons enhanced or attenuated KCl-evoked Ca2+ influx; these effects were linked with soma size. The aim of this study was to determine how AEA or its metabolites might produce these variable responses.
Experimental approach: The whole cell patch-clamp technique and fura-2 Ca2+ imaging were used to characterize the actions of AEA on action potential firing and voltage-activated K+ currents and to determine whether AEA metabolism plays any role in its effects on cultured DRG neurons.
Key results: AEA attenuated multiple action potential firing evoked by 300 ms depolarizing current commands in a subpopulation of DRG neurons. Application of 1 mu M AEA attenuated voltage-activated K+ currents and the recovery of KCl-evoked Ca2+ transients. The insensitivity of these responses to the CB1 receptor antagonist rimonabant (100 nM) and preincubation of DRG neurons with pertussis toxin suggested that these actions are not CB1 receptor-mediated. Preincubating DRG neurons with the fatty acid amide hydrolase (FAAH) inhibitor phenylmethylsulphonyl fluoride (PMSF) attenuated the inhibitory actions of AEA on K+ currents and Ca2+ influx.
Conclusion and implications: These data suggest that the products of AEA metabolism by FAAH contribute to the attenuation of K+ conductances and altered excitability of cultured sensory neurons.
Original language | English |
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Pages (from-to) | 480-492 |
Number of pages | 13 |
Journal | British Journal of Pharmacology |
Volume | 154 |
Issue number | 2 |
Early online date | 31 Mar 2008 |
DOIs | |
Publication status | Published - May 2008 |
Keywords
- cannabinoids
- sensory neurons
- potassium channels
- anandamide
- fatty acid amide hydrolase
- phenylmethylsulphonylfluoride
- arachidonic acid
- pain
- calcium-channel currents
- in-situ hybridization
- nerve growth-factor
- cannabinoid receptor
- hippocampal-neurons
- DRG neurons
- cells
- K+
- inhibition