Cannabidiol-induced intracellular Ca2+ elevations in hippocampal cells

A J Drysdale, D Ryan, R G Pertwee, B Platt

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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 mu M) elevated intracellular Ca2+ ([Ca2+](i)) by similar to +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 mu M) and the L-type specific Ca2+ channel blocker nifedipine (20 mu M). Interestingly, intracellular store depletion with thapsigargin (2 mu M) 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 mu M), and the vanilloid receptor antagonist, capsazepine (CPZ, 1 mu M). 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. (c) 2005 Elsevier Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)621-631
Number of pages11
JournalNeuropharmacology
Volume50
Issue number5
Early online date28 Dec 2005
DOIs
Publication statusPublished - Apr 2006

Keywords

  • cannabidiol
  • calcium
  • CB1
  • vanilloid
  • voltage-gated calcium channels
  • intracellular calcium stores
  • IP3 receptors
  • ryanodine receptor
  • CANNABINOID RECEPTOR AGONISTS
  • CLOSED-HEAD INJURY
  • MOUSE VAS-DEFERENS
  • CALCIUM-CHANNELS
  • SYNAPTIC-TRANSMISSION
  • NEUROBLASTOMA-CELLS
  • SELECTIVE LIGANDS
  • INDUCED ARTHRITIS
  • NEURONS
  • RAT

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