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The xenon-mediated antagonism against the NMDA receptor is non-selective for receptors containing either NR2A or NR2B subunits in the mouse amygdala

Haseneder, Rainer and Kratzer, Stephan and Kochs, Eberhard and Höfelmann, Daniela and Auberson, Yves and Eder, Matthias and Rammes, Gerhard (2009) The xenon-mediated antagonism against the NMDA receptor is non-selective for receptors containing either NR2A or NR2B subunits in the mouse amygdala. European Journal of Pharmacology, 619 (1-3). p. 33. ISSN 00142999

Abstract

In pharmacological studies using cultured neurones or heterologous expression systems, the N-methyl-Daspartate
(NMDA) receptor has been found as a major target for the inhalational anaesthetic xenon (Xe).
NMDA receptors play a crucial role in behavioural and cellular processes related to learning and memory,
and NMDA receptor subunits type 2A (NR2A) and type 2B (NR2B) are critical determinants for synaptic
plasticity. In the present study, we investigated in an acute mouse brain slice preparation of the basolateral
amygdala whether the antagonism of Xe is subunit-selective against the NR2A or NR2B subunit. From
principal neurones, pharmacologically isolated NMDA receptor-mediated currents (p-NMDA-Cs) were
evoked upon focal photolysis of caged L-glutamate and recorded using the whole-cell patch-clamp
technique. To test whether the Xe-induced inhibition of NMDA receptor-mediated currents is selective for
NR2A or NR2B subunits, p-NMDA-Cs were recorded in the presence of the NR2A or NR2B subunit antagonists
R-S-1-4-bromophenylethylamino-2,3-dioxo-1,2,3,4-tetrahydroquinoxalin-5-yl-methylphosphonic acid
(NVP-AAM077, 50 nM) or R-R*,S*-α-4-Hydroxyphenyl-β-methyl-4-phenylmethyl-1-piperidinepropanol
hydrochloride (Ro 25-6981, 0.5 μM), respectively. The Xe-induced reduction under these conditions was
not significantly different from that without NR2A or NR2B blockade. These results provide evidence, that the
Xe-induced antagonism against NMDA receptors is non-selective against NR2A- or NR2B-containing
receptors.

Item Type: Article
Keywords: Xenon; Anaesthetic; NMDA (N-methyl-d-aspartate) receptor; Subunit; NR2A (NMDA receptor subunit type 2A); NR2B (NMDA receptor subunit type 2B)
Date Deposited: 13 Oct 2015 13:16
Last Modified: 13 Oct 2015 13:16
URI: https://oak.novartis.com/id/eprint/2995

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