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Multiple actions of anandamide on neonatal rat cultured sensory neurones

Multiple actions of anandamide on neonatal rat cultured sensory neurones 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. 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. 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 μm2), it significantly enhanced Ca2+ transients (80.26±13.12% at 1 μM), an effect that persists after pertussis toxin pretreatment. In a population of neurones of smaller somal area (279±18 μm2), AEA significantly inhibits Ca2+ transients (30.75±3.54% at 1 μM), an effect that is abolished by PTX pretreatment. Extracellular application of 100 nM AEA failed to evoke TRPV1 receptor inward currents in seven out of eight neurones that responded to capsaicin (1 μM), with a mean inward current of −0.94±0.21 nA. In contrast, intracellular application of 100 nM AEA elicited robust inward currents in ∼62% of neurones, the mean population response was −0.85±0.21 nA. When AEA was applied to the intracellular environment with capsazepine (1 μM), 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. British Journal of Pharmacology (2004) 141, 1223–1233. doi:10.1038/sj.bjp.0705723 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png British Journal of Pharmacology Wiley

Multiple actions of anandamide on neonatal rat cultured sensory neurones

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Publisher
Wiley
Copyright
2004 British Pharmacological Society
ISSN
0007-1188
eISSN
1476-5381
DOI
10.1038/sj.bjp.0705723
pmid
15023857
Publisher site
See Article on Publisher Site

Abstract

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. 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. 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 μm2), it significantly enhanced Ca2+ transients (80.26±13.12% at 1 μM), an effect that persists after pertussis toxin pretreatment. In a population of neurones of smaller somal area (279±18 μm2), AEA significantly inhibits Ca2+ transients (30.75±3.54% at 1 μM), an effect that is abolished by PTX pretreatment. Extracellular application of 100 nM AEA failed to evoke TRPV1 receptor inward currents in seven out of eight neurones that responded to capsaicin (1 μM), with a mean inward current of −0.94±0.21 nA. In contrast, intracellular application of 100 nM AEA elicited robust inward currents in ∼62% of neurones, the mean population response was −0.85±0.21 nA. When AEA was applied to the intracellular environment with capsazepine (1 μM), 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. British Journal of Pharmacology (2004) 141, 1223–1233. doi:10.1038/sj.bjp.0705723

Journal

British Journal of Pharmacology – Wiley

Published: Apr 1, 2004

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