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Cannabidiol-induced intracellular Ca2+ elevations in hippocampal cells.

Abstract

The phytocannabinoid cannabidiol (CBD) is at the forefront of therapeutic cannabinoid research due to its non-psychotropic properties. Research supports its use in a variety of disorders, yet the cellular mechanisms of its action remain unclear. In this study, the effect of CBD upon Ca2+ homeostasis in hippocampal cells was characterised. CBD (1 microM) elevated intracellular Ca2+ ([Ca2+]i) by approximately +45% of basal Ca2+ levels in both glia (77% responders) and neurones (51% responders). Responses to CBD were reduced in high excitability HEPES buffered solution (HBS), but not affected in low excitability/low Ca2+ HBS. CBD responses were also significantly reduced (by 50%) by the universal Ca2+ channel blocker cadmium (50 microM) and the L-type specific Ca2+ channel blocker nifedipine (20 microM). Interestingly, intracellular store depletion with thapsigargin (2 microM) had the most dramatic effect on CBD responses, leading on average to a full block of the response. Elevated CBD-induced [Ca2+]i responses (>+100%) were observed in the presence of the CB1 receptor antagonist, AM281 (1 microM), and the vanilloid receptor antagonist, capsazepine (CPZ, 1 microM). Overall, our data suggest that CBD modulates hippocampal [Ca2+]i homeostasis via intracellular Ca2+ stores and L-type VGCC-mediated Ca2+ entry, with tonic cannabinoid and vanilloid receptor signalling being negatively coupled to this pathway.

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  • Authors+Show Affiliations

    ,

    School of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK.

    , ,

    Source

    Neuropharmacology 50:5 2006 Apr pg 621-31

    MeSH

    Animals
    Animals, Newborn
    Cadmium
    Calcium
    Calcium Channel Blockers
    Cannabidiol
    Cells, Cultured
    Drug Interactions
    Enzyme Inhibitors
    Fura-2
    Hippocampus
    Intracellular Space
    Models, Neurological
    Morpholines
    Neuroglia
    Neurons
    Nifedipine
    Pyrazoles
    Rats
    Rats, Sprague-Dawley
    Thapsigargin
    Time Factors

    Pub Type(s)

    Comparative Study
    Journal Article

    Language

    eng

    PubMed ID

    16386766

    Citation

    Drysdale, Alison J., et al. "Cannabidiol-induced Intracellular Ca2+ Elevations in Hippocampal Cells." Neuropharmacology, vol. 50, no. 5, 2006, pp. 621-31.
    Drysdale AJ, Ryan D, Pertwee RG, et al. Cannabidiol-induced intracellular Ca2+ elevations in hippocampal cells. Neuropharmacology. 2006;50(5):621-31.
    Drysdale, A. J., Ryan, D., Pertwee, R. G., & Platt, B. (2006). Cannabidiol-induced intracellular Ca2+ elevations in hippocampal cells. Neuropharmacology, 50(5), pp. 621-31.
    Drysdale AJ, et al. Cannabidiol-induced Intracellular Ca2+ Elevations in Hippocampal Cells. Neuropharmacology. 2006;50(5):621-31. PubMed PMID: 16386766.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Cannabidiol-induced intracellular Ca2+ elevations in hippocampal cells. AU - Drysdale,Alison J, AU - Ryan,Duncan, AU - Pertwee,Roger G, AU - Platt,Bettina, Y1 - 2005/12/28/ PY - 2005/10/07/received PY - 2005/11/09/revised PY - 2005/11/15/accepted PY - 2006/1/3/pubmed PY - 2006/7/11/medline PY - 2006/1/3/entrez SP - 621 EP - 31 JF - Neuropharmacology JO - Neuropharmacology VL - 50 IS - 5 N2 - The phytocannabinoid cannabidiol (CBD) is at the forefront of therapeutic cannabinoid research due to its non-psychotropic properties. Research supports its use in a variety of disorders, yet the cellular mechanisms of its action remain unclear. In this study, the effect of CBD upon Ca2+ homeostasis in hippocampal cells was characterised. CBD (1 microM) elevated intracellular Ca2+ ([Ca2+]i) by approximately +45% of basal Ca2+ levels in both glia (77% responders) and neurones (51% responders). Responses to CBD were reduced in high excitability HEPES buffered solution (HBS), but not affected in low excitability/low Ca2+ HBS. CBD responses were also significantly reduced (by 50%) by the universal Ca2+ channel blocker cadmium (50 microM) and the L-type specific Ca2+ channel blocker nifedipine (20 microM). Interestingly, intracellular store depletion with thapsigargin (2 microM) had the most dramatic effect on CBD responses, leading on average to a full block of the response. Elevated CBD-induced [Ca2+]i responses (>+100%) were observed in the presence of the CB1 receptor antagonist, AM281 (1 microM), and the vanilloid receptor antagonist, capsazepine (CPZ, 1 microM). Overall, our data suggest that CBD modulates hippocampal [Ca2+]i homeostasis via intracellular Ca2+ stores and L-type VGCC-mediated Ca2+ entry, with tonic cannabinoid and vanilloid receptor signalling being negatively coupled to this pathway. SN - 0028-3908 UR - https://www.unboundmedicine.com/medline/citation/16386766/Cannabidiol_induced_intracellular_Ca2+_elevations_in_hippocampal_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028-3908(05)00394-1 DB - PRIME DP - Unbound Medicine ER -