The xenon-mediated antagonism against the NMDA receptor is non-selective for receptors containing either NR2A or NR2B subunits in the mouse amygdala.
In pharmacological studies using cultured neurones or heterologous expression systems, the N-methyl-d-aspartate (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*-alpha-4-Hydroxyphenyl-beta-methyl-4-phenylmethyl-1-piperidinepropanol hydrochloride (Ro 25-6981, 0.5 microM), 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.
Haseneder
Rainer
R
Department of Anaesthesiology, Klinikum rechts der Isar, Technische Universität München, Ismaninger Strasse 22, 81675 Munich, Germany. haseneder@mpipsykl.mpg.de
Kratzer
Stephan
S
Kochs
Eberhard
E
Höfelmann
Daniela
D
Auberson
Yves
Y
Eder
Matthias
M
Rammes
Gerhard
G
D000679:Amygdala / Q000187:drug effects / Q000378:metabolism*; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D004553:Electric Conductivity; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013379:Substrate Specificity; D013997:Time Factors; D014978:Xenon / Q000494:pharmacology*
D018685:Anesthetics, Inhalation; D016194:Receptors, N-Methyl-D-Aspartate; D014978:Xenon; C121001:NR2B NMDA receptor