Canna~Fangled Abstracts

Nonpsychotropic Plant Cannabinoids, Cannabidivarin (CBDV) and Cannabidiol (CBD), Activate and Desensitize Transient Receptor Potential Vanilloid 1 (TRPV1) Channels in Vitro: Potential for the Treatment of Neuronal Hyperexcitability.

By July 29, 2014No Comments

Research Article

 

ACS thumbnail siteNonpsychotropic Plant Cannabinoids, Cannabidivarin (CBDV) and Cannabidiol (CBD), Activate and Desensitize Transient Receptor Potential Vanilloid 1 (TRPV1) Channels in Vitro: Potential for the Treatment of Neuronal Hyperexcitability

† Endocannabinoid Research Group, Institute of Biomolecular Chemistry (ICB), National Council of Research (CNR), 80078 Pozzuoli (NA) Italy
‡ School of Pharmacy, University of Reading, Whiteknights, Reading, RG6 6AJ, United Kingdom
Science of Health Department, §School of Pharmacy and ∥School of Medicine, University of Catanzaro, 88100 Catanzaro, Italy
ACS Chem. Neurosci., Article ASAP
DOI: 10.1021/cn5000524
Publication Date (Web): July 16, 2014
Copyright © 2014 American Chemical Society
*Mailing address: Endocannabinoid Research Group, Institute of Biomolecular Chemistry (ICB), National Council of Research (CNR), Via Campi Flegrei 34, Comprensorio Olivetti, 80078, Pozzuoli (NA) Italy. Tel: +39-081-8675093. Fax: +39-081-8041770. E-mail: vdimarzo@icb.cnr.it , *Mailing address: School of Pharmacy, University of Reading, Whiteknights, PO Box 228, Reading RG6 6AJ, UK. Tel: +44 118 378 6156. Fax: +44-118-3786542. E-mail: g.j.stephens@reading.ac.uk.

Abstract

Icon for American Chemical SocietyEpilepsy is the most common neurological disorder, with over 50 million people worldwide affected. Recent evidence suggests that the transient receptor potential cation channel subfamily V member 1 (TRPV1) may contribute to the onset and progression of some forms of epilepsy. Since the two nonpsychotropic cannabinoids cannabidivarin (CBDV) and cannabidiol (CBD) exert anticonvulsant activity in vivo and produce TRPV1-mediated intracellular calcium elevation in vitro, we evaluated the effects of these two compounds on TRPV1 channel activation and desensitization and in an in vitro model of epileptiform activity. Patch clamp analysis in transfected HEK293 cells demonstrated that CBD and CBDV dose-dependently activate and rapidly desensitize TRPV1, as well as TRP channels of subfamily V type 2 (TRPV2) and subfamily A type 1 (TRPA1). TRPV1 and TRPV2 transcripts were shown to be expressed in rat hippocampal tissue. When tested on epileptiform neuronal spike activity in hippocampal brain slices exposed to a Mg2+-free solution using multielectrode arrays (MEAs), CBDV reduced both epileptiform burst amplitude and duration. The prototypical TRPV1 agonist, capsaicin, produced similar, although not identical effects. Capsaicin, but not CBDV, effects on burst amplitude were reversed by IRTX, a selective TRPV1 antagonist. These data suggest that CBDV antiepileptiform effects in the Mg2+-free model are not uniquely mediated via activation of TRPV1. However, TRPV1 was strongly phosphorylated (and hence likely sensitized) in Mg2+-free solution-treated hippocampal tissue, and both capsaicin and CBDV caused TRPV1 dephosphorylation, consistent with TRPV1 desensitization. We propose that CBDV effects on TRP channels should be studied further in different in vitro and in vivo models of epilepsy.

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