Neuroscience 2004 Abstract
| Presentation Number: | 961.15 |
|---|---|
| Abstract Title: | CB1 cannabinoid receptor activation by an aminoalkylindole, WIN 55,212-2, increases intracellular calcium. |
| Authors: |
Lauckner, J. E.*1
; Hille, B.1
; Mackie, K.1
1Physiology and Biophysics, Univ. of Washington, Seattle, WA |
| Primary Theme and Topics |
Synaptic Transmission and Excitability - G-Protein linked Receptors -- Other |
| Session: |
961. GPCR-Linked Receptors: Other Poster |
| Presentation Time: | Wednesday, October 27, 2004 3:00 PM-4:00 PM |
| Location: | San Diego Convention Center - Hall A-H, Board # N5 |
| Keywords: | G-protein, photometry |
CNS responses to cannabis are mediated by the G protein-coupled CB1 receptor. CB1 is known to couple preferentially to Gi/Go G proteins, inhibiting calcium channels, among other actions. Here we used calcium photometry to monitor the effect of CB1 activation on intracellular calcium concentration. Local perfusion with 5 micromolar of the CB1 aminoalkylindole (AAI) agonist, WIN55,212-2 (WIN), increased intracellular calcium by several hundred nM in HEK293 cells stably expressing CB1 receptors and in cultured hippocampal neurons. The calcium increase was blocked by co-incubation with the CB1 receptor antagonist, SR141716A, and was absent in non-transfected HEK293 cells as well as in hippocampal neurons cultured from CB1 knockout mice. The calcium rise was WIN-specific, being absent in cells treated with other classes of cannabinoid agonists including delta-9-tetrahydrocannabinol and HU210 (classical cannabinoids), CP55,940 (a non-classical cannabinoid) and methanandamide (an eicosanoid cannabinoid) and the non-CB1 binding isomer of WIN, WIN55,212-3. In contrast to other CB1 mediated-effects, the increase in calcium elicited by WIN activation of CB1 receptors was independent of Gi/Go proteins as it was present in pertussis toxin (PTX)-treated cells. Indeed, PTX pretreatment led to a more potent, rapid and extensive increase in intracellular calcium compared to non-PTX-treated cells. WIN increases in intracellular calcium appear to be mediated by Gq G proteins as they were markedly attenuated in cells transfected with either dominant negative Gq or RGS2. WIN likely releases calcium from intracellular stores as the increase was blocked by thapsigargin, but not by removal of extracellular calcium. In summary, these results suggest that the AAI, WIN, stabilizes CB1 receptors in a conformation that activates Gq signaling pathways.
Supported by DA11322, DA09158, NS08174
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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