Neuroscience 2003 Abstract
| Presentation Number: | 264.16 |
|---|---|
| Abstract Title: | Tropisetron protects isolated adult pig retinal ganglion cells from glutamate-induced excitotoxicity through α7 nicotinic ACh receptors. |
| Authors: |
Linn, C. L.*1
; Linn, D. M.1,2
1Biological Sci., Western Michigan Univ., Kalamazoo, MI 2MI, 1903 West Michigan Ave., 49008, |
| Primary Theme and Topics |
Sensory Systems - Vision -- Retina and photoreceptors |
| Session: |
264. Retina: Ganglion Cells Poster |
| Presentation Time: | Sunday, November 9, 2003 4:00 PM-5:00 PM |
| Location: | Morial Convention Center - Hall F-I, Board # E17 |
| Keywords: | CELL CULTURE, EXCITATORY AMINO ACID, NEUROPROTECTION |
Tropisetron is widely regarded as a potent and selective 5-HT3 antagonist used to treat nausea and emesis in cancer patients undergoing radiation and chemotherapy. Recently, it has been demonstrated that tropisetron may also be an agonist for the α7 nAChR. Tropisetron exhibited high affinity binding for α7 nAChRs labeled with [3H]-methyllycaconitine (MLA) and evoked electrophysiological responses in primary rat hippocampal neurons that were blocked by MLA in the low nanomolar concentration range (Cortes-Burgos et al., SFN, 2001). To explore the potential role of tropisetron as an α7 nAChR agonist in the retina, we have investigated the neuroprotective effect of tropisetron on glutamate-induced excitotoxicity in cultured adult pig retinal ganglion cells (RGCs) isolated through a “panning” technique. In this model system, glutamate-induced excitotoxicity (500 μM) was eliminated in the presence of 5 μM ACh. Blockade of this effect with α-bungarotoxin (α-BTX) and MLA indicate an α7 nAChR-dependent mechanism (Wehrwein et al., SFN, 2002). To determine if tropisetron could mimic the neuroprotective effect of ACh, various concentrations of tropisetron were applied to panned adult pig RGCs two hours before application of 500 μM L-glutamate. After 3 days of chronic exposure, cultured cells were loaded with 2 μM calcein, counted and compared to results with RGCs exposed to ACh. 100 nM tropisetron exhibited a maximal effect and inhibited the excitotoxic effect of 500 μM glutamate by 82% (± 4.2), compared to a 98% (± 4.3) neuroprotective effect associated with 5 μM ACh. The effects of tropisetron were significantly reduced in the presence of α-BTX and MLA, but not in the presence of the 5-HT3 selective antagonist, tropine. These results support the hypothesis that tropisetron acts as an agonist at α7 nAChRs on pig RGCs.
Supported by WMU Neuroscience Jumpstart Award to C.L. Linn
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2003 Neuroscience Meeting Planner. New Orleans, LA: Society for Neuroscience, 2003. Online.
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