Neuroscience 2003 Abstract
| Presentation Number: | 683.1 |
|---|---|
| Abstract Title: | Differential effects of synthetic and endogenous cannabinoid receptor ligands on α7-nicotinic acetylcholine receptor-mediated currents in <I>Xenopus</I> oocytes. |
| Authors: |
Spivak, C. E.*1
; Oz, M.1
; Morales, M.1
; Lupica, C. R.1
1Cell. Neurophysiol. Unit, NIDA-IRP, NIH, DHHS, Baltimore, MD |
| Primary Theme and Topics |
Synaptic Transmission and Excitability - Ligand Gated Ion Channels -- Nicotinic acetylcholine receptors |
| Secondary Theme and Topics | Neurological and Psychiatric Conditions<br />- Addiction and Drugs of Abuse<br />-- Opioids and others |
| Session: |
683. Neuronal nAChRs: Addictive, Anesthetic, & Other Drug Interactions Poster |
| Presentation Time: | Tuesday, November 11, 2003 1:00 PM-2:00 PM |
| Location: | Morial Convention Center - Hall F-I, Board # C60 |
| Keywords: | ACETYLCHOLINE, DRUG ABUSE |
The effect of cannabinoid receptor ligands including 2-arachidonylglycerol, anandamide, methanandamide, Δ9-THC, WIN 55,212-2 and CP 55,940 on the function of homomeric α7 nicotinic ACh receptors expressed in Xenopus oocytes was investigated using the two-electrode voltage-clamp technique. The endogenous cannabinoid receptor ligands 2-arachidonylglycerol, anandamide and methanandamide inhibited currents evoked with ACh (100 μM). The inhibitory effects of all endogenous ligands tested developed gradually, reaching maximum within 20 to 30 min and was fully reversible following 10 to 30 min of washout. The IC50 values for 2-arachidonylglycerol, anandamide and methanandamide were 110, 218 nM and 103 nM, respectively. In contrast, the synthetic cannabinoid receptor agonists CP 55,940 and WIN 55,212-2, and the active ingredient of marijuana, Δ9-THC, inhibited these currents only at much higher concentrations (1 μM to 100 μM). The inhibition of α7-mediated currents by 2-arachidonylglycerol was non-competitive and voltage-independent, and the effects of 2-arachidonylglycerol and anandamide were not mediated by CB1 or CB2 receptors, as neither the selective CB1 receptor antagonist SR 141716A nor CB2 receptor antagonist SR 144528 reduced the inhibition by these ligands. Furthermore, the anandamide transport inhibitor AM404 did not prevent inhibition by either 2-arachidonylglycerol or anandamide of the nicotinic responses In conclusion, the data indicate that endogenous cannabinoid receptor ligands can potently inhibit α7-nicotinic ACh receptor function independently of cannabinoid receptors, whereas synthetic cannabinoid ligands appear to be relatively ineffective at inhibiting these receptors.
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2003 Neuroscience Meeting Planner. New Orleans, LA: Society for Neuroscience, 2003. Online.
Copyright © 2003-2025 Society for Neuroscience; all rights reserved. Permission to republish any abstract or part of any abstract in any form must be obtained in writing by SfN office prior to publication.
