Please use this identifier to cite or link to this item: http://hdl.handle.net/10397/33513
Title: Mecamylamine prevents neuronal apoptosis induced by glutamate and low potassium via differential anticholinergic-independent mechanisms
Authors: Fu, H
Dou, J
Li, W
Luo, J
Li, KC
Lam, CSC
Lee, NTK
Li, M
Han, Y 
Keywords: Apoptosis
Glutamate
JNK/c-Jun pathway
Low potassium
Mecamylamine
NMDA receptors
Issue Date: 2008
Publisher: Pergamon-Elsevier Science Ltd
Source: Neuropharmacology, 2008, v. 54, no. 4, p. 755-765 How to cite?
Journal: Neuropharmacology 
Abstract: Neuronal loss via apoptosis caused by various stimuli may be the fundamental mechanism underlying chronic and acute neurodegenerative diseases. A drug inhibiting neuronal apoptosis may lead to a practical treatment for these diseases. In this study, treatment with mecamylamine, a classical antagonist of nicotinic acetylcholine receptors (nAChRs), prevented neuronal apoptosis induced by 75 μM glutamate and by low potassium (LK) in cerebellar granule neurons (CGNs) with EC 50s of 35 and 293 μM, respectively. Two other antagonists of nAChRs, dihydro-β-erythroidine and tubocurarine, failed to inhibit these two kinds of apoptosis. Mecamylamine inhibited the NMDA (30 μM)-evoked current and competed with [ 3H]MK-801. Furthermore, two inhibiters of the c-Jun N-terminal kinase (JNK) pathway prevented LK-induced apoptosis. Mecamylamine reversed the phosphorylation levels of JNK and c-Jun as well as the expression of c-Jun caused by LK in a Western blot assay. In addition, the JNK/c-Jun pathway was not involved in glutamate-induced cell death of CGNs. Our results suggest that mecamylamine prevents glutamate-induced apoptosis by blocking NMDA receptors at the MK-801 site and LK-induced apoptosis by inhibiting the activation of the JNK/c-Jun pathway.
URI: http://hdl.handle.net/10397/33513
DOI: 10.1016/j.neuropharm.2007.12.003
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