RGD Reference Report - Inhibition by 2-methoxy-4-ethylphenol of Ca2+ influx through acquired and native N-methyl-D-aspartate-receptor channels. - Rat Genome Database

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Inhibition by 2-methoxy-4-ethylphenol of Ca2+ influx through acquired and native N-methyl-D-aspartate-receptor channels.

Authors: Fukumori, R  Nakamichi, N  Takarada, T  Kambe, Y  Matsushima, N  Moriguchi, N  Yoneda, Y 
Citation: Fukumori R, etal., J Pharmacol Sci. 2010 Mar 19;112(3):273-81. Epub 2010 Feb 18.
RGD ID: 2325881
Pubmed: PMID:20168047   (View Abstract at PubMed)

Pharmacological properties were evaluated for the antidiarrheic wood creosote ingredient 2-methoxy-4-ethylphenol (2M4EP), which was shown to be protective against neurotoxicity of N-methyl-D-aspartate (NMDA), to modulate Ca(2+) influx across acquired and native NMDA receptor (NMDAR) channels. NMDA markedly increased intracellular free Ca(2+) levels in HEK293 cells transfected with the expression vector of either NR2A or NR2B subunit together with the essential NR1 subunit vector. Further addition of dizocilpine inhibited the increase by NMDA in intracellular Ca(2+) levels in both types of acquired NMDAR channels, while 2M4EP and the NR2B-subunit-selective antagonist ifenprodil were more effective in inhibiting the increase by NMDA in HEK293 cells expressing NR1/NR2B subunits than in those with NR1/NR2A subunits. 2M4EP significantly prevented the increased intracellular Ca(2+) levels by NMDA in cultured rat hippocampal neurons. Brief exposure to NMDA led to a drastic decrease in cellular viability 24 h later in cultured hippocampal neurons, while 2M4EP significantly prevented the loss of cellular vitality by NMDA. Similarly, 2M4EP more efficiently protected HEK293 cells with NR1/NR2B subunits than those with NR1/NR2A subunits. These results suggest that 2M4EP may protect neurons from excitotoxicity through inhibition of Ca(2+) influx across NMDAR channels composed of NR1/NR2B, rather than NR1/NR2A, subunits.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
intracellular calcium ion homeostasis  IMP 2325881 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Grin2b  (glutamate ionotropic receptor NMDA type subunit 2B)

Objects referenced in this article
Gene Grin1 glutamate ionotropic receptor NMDA type subunit 1 Rattus norvegicus
Gene Grin2a glutamate ionotropic receptor NMDA type subunit 2A Rattus norvegicus

Additional Information