Mecamylamine prevents neuronal apoptosis induced by glutamate and low potassium via differential anticholinergic-independent mechanisms

Hongjun Fu, Juan Dou, Wenming Li, Jialie Luo, Kenny C. Li, Colin S.C. Lam, Nelson T.K. Lee, Mingtao Li, Yifan Han

Research output: Journal article publicationJournal articleAcademic researchpeer-review

13 Citations (Scopus)


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 EC50s 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.
Original languageEnglish
Pages (from-to)755-765
Number of pages11
Issue number4
Publication statusPublished - 1 Mar 2008


  • Apoptosis
  • Glutamate
  • JNK/c-Jun pathway
  • Low potassium
  • Mecamylamine
  • NMDA receptors

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

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