TY - JOUR
T1 - Inhibition by 2-methoxy-4-ethylphenol of Ca2+ influx through acquired and native N-methyl- D-aspartate-receptor channels
AU - Fukumori, Ryo
AU - Nakamichi, Noritaka
AU - Takarada, Takeshi
AU - Kambe, Yuki
AU - Matsushima, Nobuyuki
AU - Moriguchi, Nobuaki
AU - Yoneda, Yukio
N1 - Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2010/3/19
Y1 - 2010/3/19
N2 - 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 Ca2+ influx across acquired and native NMDA re-ceptor (NMDAR) channels. NMDA markedly increased intracellular free Ca2+ 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 Ca2+ 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 Ca2+ levels by NMDA in cultured rat hippocam-pal 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 Ca2+ influx across NMDAR channels composed of NR1/ NR2B, rather than NR1/NR2A, subunits.
AB - 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 Ca2+ influx across acquired and native NMDA re-ceptor (NMDAR) channels. NMDA markedly increased intracellular free Ca2+ 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 Ca2+ 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 Ca2+ levels by NMDA in cultured rat hippocam-pal 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 Ca2+ influx across NMDAR channels composed of NR1/ NR2B, rather than NR1/NR2A, subunits.
KW - Acquired channel
KW - Antidiarrheic
KW - Hippocampal neuron
KW - N-methyl-D-aspartate receptor
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U2 - 10.1254/jphs.09294FP
DO - 10.1254/jphs.09294FP
M3 - Article
C2 - 20168047
AN - SCOPUS:77950639141
VL - 112
SP - 273
EP - 281
JO - Journal of Pharmacological Sciences
JF - Journal of Pharmacological Sciences
SN - 1347-8648
IS - 3
ER -