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Chronic exposure of sensory neurones to increased levels of nerve growth factor modulates CB 1 /TRPV1 receptor crosstalk
Author(s) -
Evans R M,
Scott R H,
Ross R A
Publication year - 2007
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0707411
Subject(s) - nerve growth factor , endocrinology , medicine , trpv1 , chemistry , agonist , cannabinoid receptor , dorsal root ganglion , cannabinoid , receptor , antagonist , electrophysiology , sensory system , biology , transient receptor potential channel , neuroscience
Background: Anandamide (AEA) activates both cannabinoid CB 1 and TRPV1 receptors, which are expressed on cultured dorsal root ganglion neurones. Increased levels of nerve growth factor (NGF) are associated with chronic pain states. Experimental approach: The aim of this study was to compare of the effects of AEA on CB 1 receptor signalling and TRPV1‐CB 1 crosstalk in low and high concentrations of NGF, using voltage‐clamp electrophysiology and Fura‐2 calcium imaging. Key results: Chronic exposure to high NGF (200 ng ml −1 ) as compared to low NGF (20 ng ml −1 ) increases the proportion of neurones that exhibit an inward current in response to AEA (1 μ M ), from 7 to 29%. In contrast, inhibition of voltage‐gated calcium currents by AEA is not significantly different in low NGF (33±9%, compared to high NGF 28±6%). Crosstalk between CB and TRPV1 receptors is modulated by exposure to high NGF. In low NGF, exposure to the CB 1 receptor antagonist, SR141716A, (100 n M ) increases the percentage of neurones in which AEA elicits an increase in [Ca 2+ ] i , from 10 to 23%. In high NGF, the antagonist does not alter the percentage of responders (33 to 30%). In low NGF, exposure to the CB receptor agonist, WIN55 (1 μ M ) reduces capsaicin‐mediated increases in [Ca 2+ ] i to 28±8% of control as compared to an enhancement to 172±26% of control observed in high NGF. Conclusions and implications: We conclude that cannabinoid‐mediated modulation of TRPV1 receptor activation is altered after exposure to high NGF. British Journal of Pharmacology (2007) 152 , 404–413; doi: 10.1038/sj.bjp.0707411 ; published online 13 August 2007