Neuroscience 2004 Abstract
| Presentation Number: | 690.9 |
|---|---|
| Abstract Title: | Regulation of intracellular calcium stores by the plant cannabinoid, cannabidiol. |
| Authors: |
Drysdale, A. J.*1
; Pertwee, R. G.1
; Platt, B.1
1Sch. of Med. Sci., Univ. of Aberdeen, Aberdeen, United Kingdom |
| Primary Theme and Topics |
Neurological and Psychiatric Conditions - Addiction and Drugs of Abuse -- Cannabinoids |
| Secondary Theme and Topics | Synaptic Transmission and Excitability<br />- Ion Channels<br />-- Calcium Channels: Pharmacology |
| Session: |
690. Drugs of Abuse: Cannabinoids Poster |
| Presentation Time: | Tuesday, October 26, 2004 8:00 AM-9:00 AM |
| Location: | San Diego Convention Center - Hall A-H, Board # EEE10 |
| Keywords: | FURA-2, G PROTEIN, HIPPOCAMPUS, RECEPTOR |
Current findings demonstrate that cannabinoids (CBs) can elicit both neuroprotection and neuromodulation, although detailed mechanisms remain to be elucidated. Here we investigated whether the non-psychotropic plant cannabinoid, cannabidiol (CBD), can modulate Ca2+ signalling in hippocampal cells.
Hippocampi of Sprague-Dawley neonates (1-3 days) were dissected and the tissue enzymatically dissociated. Cultures were matured for 5-12 days and loaded with the fluorescent Ca2+ indicator Fura-2AM (6–10 µM). Dishes were perfused with HEPES buffered solution (containing 0.5 µM TTX) and images captured at 350 and 380 nm to calculate [Ca2+]i measurements as ratio units.
CBD application (1 µM) induced a Ca2+ response in both neurones and glia (46% and 83%, respectively). Interestingly, the CBD-induced Ca2+ response was significantly enhanced by the CB1 antagonist AM281 (1 µM, 400%) and in cultures pre-incubated with the Gi/o protein blocker, pertussis toxin (PTX, 100 ng/ml, 300%), indicative of a CB1 receptor dependent pathway counteracting CBD's Ca2+ releasing action. Studies with thapsigargin (2 µM), used to deplete [Ca2+]i stores, demonstrated the dependence of the CBD-induced Ca2+ rise upon these stores. This link, however, did not involve activation of phospholipase C, since pre-incubation with the inhibitor U73122 (100 nM) did not prevent, but rather significantly increased, the CBD response. Since the Ca2+ channel blockers, nifedipine and cadmium, also significantly reduced the CBD-induced Ca2+ response, we propose that CBD may act to regulate Ca2+-induced Ca2+ release.
In conclusion, we show that CBD can raise [Ca2+]i via a CB1 receptor independent pathway, while CB1 receptor signalling affects this action negatively. The outlined mechanisms may contribute to the proposed neuroprotective activity of CBD with regards to the regulation of Ca2+ homeostasis in neurones.
The supply of CBD from GW Pharmaceuticals is acknowledged.
Hippocampi of Sprague-Dawley neonates (1-3 days) were dissected and the tissue enzymatically dissociated. Cultures were matured for 5-12 days and loaded with the fluorescent Ca2+ indicator Fura-2AM (6–10 µM). Dishes were perfused with HEPES buffered solution (containing 0.5 µM TTX) and images captured at 350 and 380 nm to calculate [Ca2+]i measurements as ratio units.
CBD application (1 µM) induced a Ca2+ response in both neurones and glia (46% and 83%, respectively). Interestingly, the CBD-induced Ca2+ response was significantly enhanced by the CB1 antagonist AM281 (1 µM, 400%) and in cultures pre-incubated with the Gi/o protein blocker, pertussis toxin (PTX, 100 ng/ml, 300%), indicative of a CB1 receptor dependent pathway counteracting CBD's Ca2+ releasing action. Studies with thapsigargin (2 µM), used to deplete [Ca2+]i stores, demonstrated the dependence of the CBD-induced Ca2+ rise upon these stores. This link, however, did not involve activation of phospholipase C, since pre-incubation with the inhibitor U73122 (100 nM) did not prevent, but rather significantly increased, the CBD response. Since the Ca2+ channel blockers, nifedipine and cadmium, also significantly reduced the CBD-induced Ca2+ response, we propose that CBD may act to regulate Ca2+-induced Ca2+ release.
In conclusion, we show that CBD can raise [Ca2+]i via a CB1 receptor independent pathway, while CB1 receptor signalling affects this action negatively. The outlined mechanisms may contribute to the proposed neuroprotective activity of CBD with regards to the regulation of Ca2+ homeostasis in neurones.
The supply of CBD from GW Pharmaceuticals is acknowledged.
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2004 Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience, 2004. Online.
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