Cannabidiol-induced intracellular Ca2+ elevations in hippocampal cells.
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.
Drysdale
Alison J
AJ
School of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK.
Ryan
Duncan
D
Pertwee
Roger G
RG
Platt
Bettina
B
D000818:Animals; D000831:Animals, Newborn; D002104:Cadmium / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002185:Cannabidiol / Q000494:pharmacology*; D002478:Cells, Cultured; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016257:Fura-2 / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D006624:Hippocampus / Q000166:cytology*; D042541:Intracellular Space / Q000187:drug effects*; D008959:Models, Neurological; D009025:Morpholines / Q000494:pharmacology; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019284:Thapsigargin / Q000494:pharmacology; D013997:Time Factors
D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D009025:Morpholines; D011720:Pyrazoles; D002104:Cadmium; C049925:fura-2-am; D002185:Cannabidiol; D019284:Thapsigargin; D009543:Nifedipine; C109925:AM 281; D002118:Calcium; D016257:Fura-2