Neuroscience 2005 Abstract
| Presentation Number: | 511.19 |
|---|---|
| Abstract Title: | CB1 receptor antagonists uncover an inhibitory effect of anandamide on medium-size dorsal root ganglion neurons. |
| Authors: |
Seybold, V. S.*1
; Khasabova, I. A.2
; Simone, D. A.2
1Neurocience, Univ. of Minnesota, Minneapolis, MN 2Oral Science, Univ. of Minnesota, Minneapolis, MN |
| Primary Theme and Topics |
Sensory and Motor Systems - Pain -- Spinal cord processing: Pharmacology |
| Session: |
511. Nociceptors: Mediators and Modulation Poster |
| Presentation Time: | Monday, November 14, 2005 3:00 PM-4:00 PM |
| Location: | Washington Convention Center - Hall A-C, Board # X19 |
| Keywords: | CANNABINOIDS, CALCIUM CHANNEL |
Although inverse agonist properties are attributed to the cannabinoid-1 receptor (CB1R) antagonist SR141716A, no independent effect has been observed for this ligand in the bioassay of cannabinoid inhibition of the KCl-evoked increase in free intacellular calcium concentration ([Ca2+]i) measured by microfluorimetry in either rat (Khasabova et. al., 2002) or mouse (Khasabova et al., 2005, SFN abstract) dissociated dorsal root ganglion (DRG) neurons in vitro. In this model, SR141716A effectively blocks the inhibitory effect of synthetic CB1R agonists on medium-large size DRG neurons. In recent studies of endocannabinoids on DRG neurons, anandamide (AEA) alone had no effect on this population of DRG neurons, but SR141716A+AEA resulted in inhibition of the KCl-evoked increase in [Ca2+]i. Responses to another CB1R antagonist, AM251, in the absence and presence of AEA paralleled responses to SR141716A suggesting that the ability of CB1R antagonists to uncover an effect of AEA is not specific to one drug but rather is a function of the CB1R protein. In contrast to the inhibitory effect of CB1R agonists in this same population of DRG neurons, the inhibitory effect of SR141716A+AEA is not mediated by G-proteins because it is not blocked by pertusis toxin. Interestingly, methyl-β-cyclodextrin (1 mM), which depletes membrane cholesterol, blocked the effect of SR141716A but did not block the inhibitory effect of the synthetic CB1R agonist ACEA.
Together these data suggest that a basal coupling of Gi/Go to voltage-dependent calcium channels (VDCC) in DRG neurons masks the access of AEA to a site that inhibits their function. However, in the presence of CB1R antagonists, the CB1R/G-protein complex may be stabilized thereby allowing AEA access to inhibition of voltage-dependent calcium channels through a lipid membrane domain.
Together these data suggest that a basal coupling of Gi/Go to voltage-dependent calcium channels (VDCC) in DRG neurons masks the access of AEA to a site that inhibits their function. However, in the presence of CB1R antagonists, the CB1R/G-protein complex may be stabilized thereby allowing AEA access to inhibition of voltage-dependent calcium channels through a lipid membrane domain.
Supported by DA11471 (DS)
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2005 Neuroscience Meeting Planner. Washington, DC: Society for Neuroscience, 2005. Online.
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