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• W2090598851 abstract "1 The effect of 5-HT and related indolealkylamines on heteromeric recombinant NMDA receptors expressed in Xenopus oocytes was investigated using the two-electrode voltage-clamp recording technique. 2 In the absence of external Mg2+ ions, 5-HT inhibited NMDA receptor-mediated currents in a concentration-dependent manner. The inhibitory effect of 5-HT was independent of the NR1a and NR2 subunit combination. 3 The inhibition of glutamate-evoked currents by 5-HT was use- and voltage-dependent. The voltage sensitivity of inhibition for NR1a+NR2 subunit combinations by 5-HT was similar, exhibiting an e-fold change per ∼20 mV, indicating that 5-HT binds to a site deep within the membrane electric field. 4 The inhibition of the open NMDA receptor by external Mg2+ and 5-HT was not additive, suggesting competition between Mg2+ and 5-HT for a binding site in the NMDA receptor channel. The concentration-dependence curves for 5-HT and 5-methoxytryptamine (5-MeOT) inhibition of NMDA receptor-mediated currents are shifted to the right in the presence of external Mg2+. 5 The related indolealkylamines inhibited glutamate-evoked currents with the following order of inhibitory potency: 5-MeOT=5-methyltryptamine>tryptamine>7-methyltryptamine>5-HT≫tryptophan=melatonin. 6 Taken together, these data suggest that 5-HT and related compounds can attenuate glutamate-mediated excitatory synaptic responses and may provide a basis for drug treatment of excitoxic neurodegeneration. British Journal of Pharmacology (2005) 144, 323–330. doi:10.1038/sj.bjp.0706049" @default.
• W2090598851 created "2016-06-24" @default.
• W2090598851 creator A5025386235 @default.
• W2090598851 creator A5070282013 @default.
• W2090598851 date "2005-02-01" @default.
• W2090598851 modified "2023-09-27" @default.
• W2090598851 title "Voltage-dependent inhibition of recombinant NMDA receptor-mediated currents by 5-hydroxytryptamine" @default.
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• W2090598851 doi "https://doi.org/10.1038/sj.bjp.0706049" @default.
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