Neuroscience 2001 Abstract
| Presentation Number: | 805.8 |
|---|---|
| Abstract Title: | Inhibition By Cannabinoid<sub>1</sub> Receptor Agonists Of Currents Through Human 5-HT<sub>3A</sub> Receptors. |
| Authors: |
Barann, M.*1,2
; Molderings, G.2
; Urban, B. W.1
; Gothert, M.2
1Anesthesiology, University of Bonn, Bonn, Germany 2Germany, University of Bonn, Bonn, Germany |
| Primary Theme and Topics |
Synaptic Transmission and Excitability - Neurotransmitters -- Cannabinoids |
| Secondary Theme and Topics | Synaptic Transmission and Excitability<br />- Ligand Gated Ion Channels<br />-- 5-HT3 receptors |
| Session: |
805. Neurotransmitters: cannabinoids Poster |
| Presentation Time: | Wednesday, November 14, 2001 4:00 PM-5:00 PM |
| Location: | Exhibit Hall D-28 |
| Keywords: | Cannabinoids, Serotonin, Patch Clamp, Binding |
Patch clamping (excised patches) and radioligand binding techniques (membranes) were used to study effects of cannabinoid1receptor (CB1R) agonists on human 5-HT3A receptors (h5-HT3AR), stably transfected in HEK-293 cells. At negative membrane potentials, 5-HT induced concentration-dependent currents (EC50 value 9 μM) sensitive to blockade by 0.3 nM ondansetron. The CB1R agonists delta-9-tetrahydrocannabinol (IC50: 0.04 μM), WIN 55212-2 (IC50: 0.1 μM), anandamide (IC50: 0.2 μM) and CP55940
(IC50: 0.7 μM) concentration-dependently inhibited 5-HT (30 µM)-induced currents, whereas WIN 55212-3 (an enantiomer of WIN 55212-2) at up to 1 μM did not. The CB1R antagonist SR141716 (1 μM) failed to counteract the almost complete blockade by 1 μM WIN 55212-2. In non-transfected HEK-293 cells, virtually no mRNA for CB1R was present and in membranes prepared from such cells no specific [3H]SR141716 binding was detectable. In membranes from cells expressing the h5-HT3AR, the CB1R ligands WIN 55212-2, CP55940 and SR141716 failed to inhibit specific [3H]GR65630 binding to the h5-HT3AR. In agreement with results in rat nodose ganglion (J. Neurophysiol., 73: 907-910, 1995) CB1R agonists stereoselectively inhibit currents through 5-HT3R channels. This inhibition may contribute to the analgesic and antiemetic effects of cannabinoid receptor ligands.The effect of CB1R ligands on h5-HT3AR is mediated neither by CB1R nor an action at the ligand recognition site of the h-HT3AR. An action via a modulatory site on the h5-HT3AR is conceivable.
(IC50: 0.7 μM) concentration-dependently inhibited 5-HT (30 µM)-induced currents, whereas WIN 55212-3 (an enantiomer of WIN 55212-2) at up to 1 μM did not. The CB1R antagonist SR141716 (1 μM) failed to counteract the almost complete blockade by 1 μM WIN 55212-2. In non-transfected HEK-293 cells, virtually no mRNA for CB1R was present and in membranes prepared from such cells no specific [3H]SR141716 binding was detectable. In membranes from cells expressing the h5-HT3AR, the CB1R ligands WIN 55212-2, CP55940 and SR141716 failed to inhibit specific [3H]GR65630 binding to the h5-HT3AR. In agreement with results in rat nodose ganglion (J. Neurophysiol., 73: 907-910, 1995) CB1R agonists stereoselectively inhibit currents through 5-HT3R channels. This inhibition may contribute to the analgesic and antiemetic effects of cannabinoid receptor ligands.The effect of CB1R ligands on h5-HT3AR is mediated neither by CB1R nor an action at the ligand recognition site of the h-HT3AR. An action via a modulatory site on the h5-HT3AR is conceivable.
Supported by Deutsche Forschungsgemeinschaft (DFG)
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2001 Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience, 2001. Online.
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