The Experts below are selected from a list of 112782 Experts worldwide ranked by ideXlab platform

Sic L Chan - One of the best experts on this subject based on the ideXlab platform.

  • dapk1 interaction with NMDA Receptor nr2b subunits mediates brain damage in stroke
    Cell, 2010
    Co-Authors: Weihong Tu, Mangala M Soundarapandian, Cherine Balel, Manqi Wang, Lisheng Peng, Wenfeng Zhang, Xiaofen Zhong, Xin Xu, Wen Zhang, Sic L Chan
    Abstract:

    Summary N -methyl- D -aspartate (NMDA) Receptors constitute a major subtype of glutamate Receptors at extrasynaptic sites that link multiple intracellular catabolic processes responsible for irreversible neuronal death. Here, we report that cerebral ischemia recruits death-associated protein kinase 1 (DAPK1) into the NMDA Receptor NR2B protein complex in the cortex of adult mice. DAPK1 directly binds with the NMDA Receptor NR2B C-terminal tail consisting of amino acid 1292-1304 (NR2B CT ). A constitutively active DAPK1 phosphorylates NR2B subunit at Ser-1303 and in turn enhances the NR1/NR2B Receptor channel conductance. Genetic deletion of DAPK1 or administration of NR2B CT that uncouples an activated DAPK1 from an NMDA Receptor NR2B subunit in vivo in mice blocks injurious Ca 2+ influx through NMDA Receptor channels at extrasynaptic sites and protects neurons against cerebral ischemic insults. Thus, DAPK1 physically and functionally interacts with the NMDA Receptor NR2B subunit at extrasynaptic sites and this interaction acts as a central mediator for stroke damage.

Gordon A Barr - One of the best experts on this subject based on the ideXlab platform.

  • Ontogeny of NMDA Receptor-mediated morphine tolerance in the postnatal rat.
    Pain, 2003
    Co-Authors: Gordon A Barr
    Abstract:

    Abstract N-methyl- d -aspartate (NMDA) Receptor antagonists are effective in inhibiting the development of morphine tolerance in adult rats. But NMDA Receptors undergo dramatic change during the first few weeks of the postnatal life in the rat, and it is unknown whether NMDA Receptor antagonists can inhibit the acquisition of opiate tolerance in the developing organism. Here, we investigated the effects of two NMDA Receptor antagonists MK-801 and dextromethorphan on the development of morphine tolerance in 7-, 14-, and 21-day-old rats. NMDA Receptor antagonists are not effective in attenuating morphine tolerance in the neonatal rat whereas they were partially effected in the 14-day-old and fully effective in rats as old or older than 21 days of age. These data suggest that there exists a transition age, around the second postnatal week in the rat, for the NMDA Receptor to play a role in the development of morphine tolerance.

David J. Adams - One of the best experts on this subject based on the ideXlab platform.

  • Polymodal Regulation of NMDA Receptor-Channels
    Channels (Austin Tex.), 2007
    Co-Authors: Anna Kloda, Boris Martinac, David J. Adams
    Abstract:

    Glutamate-activated N-methyl-D-aspartate (NMDA) Receptors are ligand-gated ion channels which mediate synaptic transmission, long-term potentiation, synaptic plasticity and neurodegeneration via conditional Ca2+ signalling. Recent crystallographic studies have focussed on solving the structural determinant of the ligand binding within the core region of NR1 and NR2 subunits. Future structural analysis will help to understand the mechanism of native channel activation and regulation during synaptic transmission. A number of NMDA Receptor ligands have been identified which act as positive or negative modulators of Receptor function. There is evidence that the lipid bilayer can further regulate the activity of the NMDA Receptor channels. Modulators of NMDA Receptor function offer the potential for the development of novel therapeutics to target neurological disorders associated with this family of glutamate ion channel Receptors. Here, we review the recent literature concerning structural and functional properties, as well as the physiological and pathological roles of NMDA Receptor channels.

Masaaki Arakawa - One of the best experts on this subject based on the ideXlab platform.

  • molecular diversity of the NMDA Receptor channel
    Nature, 1992
    Co-Authors: Tatsuya Kutsuwada, Nobuko Kashiwabuchi, Hisashi Mori, Kenji Sakimura, Etsuko Kushiya, Kazuaki Araki, Hiroyuki Meguro, Hisashi Masaki, Toshiro Kumanishi, Masaaki Arakawa
    Abstract:

    Two novel subunits of the mouse NMDA Receptor channel, the epsilon 2 and epsilon 3 subunits, have been identified by cloning and expression of complementary DNAs. The heteromeric epsilon 1/zeta 1, epsilon 2/zeta 1 and epsilon 3/zeta 1 NMDA Receptor channels exhibit distinct functional properties in affinities for agonists and sensitivities to competitive antagonists and Mg2+ block. In contrast to the wide distribution of the epsilon 1 and zeta 1 subunit messenger RNAs in the brain, the epsilon 2 subunit mRNA is expressed only in the forebrain and the epsilon 3 subunit mRNA is found predominantly in the cerebellum. The epsilon 1/zeta 1 and epsilon 2/zeta 1 channels expressed in Xenopus oocytes, but not the epsilon 3/zeta 1 channel, are activated by treatment with 12-O-tetradecanoylphorbol 13-acetate. These findings suggest that the molecular diversity of the epsilon subunit family underlies the functional heterogeneity of the NMDA Receptor channel.

  • functional characterization of a heteromeric NMDA Receptor channel expressed from cloned cdnas
    Nature, 1992
    Co-Authors: Hiroyuki Meguro, Tatsuya Kutsuwada, Hisashi Mori, Kenji Sakimura, Etsuko Kushiya, Kazuaki Araki, Toshiro Kumanishi, Masaaki Arakawa, Makoto Yamazaki, Masayoshi Mishina
    Abstract:

    The glutamate Receptor (GluR) channel plays a key part in brain function. Among GluR channel subtypes, the NMDA (N-methyl-D-aspartate) Receptor channel which is highly permeable to Ca2+ is essential for the synaptic plasticity underlying memory, learning and development. Furthermore, abnormal activation of the NMDA Receptor channel may trigger the neuronal cell death observed in various brain disorders. A complementary DNA encoding a subunit of the rodent NMDA Receptor channel (NMDAR1 or zeta 1) has been cloned and its functional properties investigated. Here we report the identification and primary structure of a novel mouse NMDA Receptor channel subunit, designated as epsilon 1, after cloning and sequencing the cDNA. The epsilon 1 subunit shows 11-18% amino-acid sequence identity with rodent GluR channel subunits that have been characterized so far and has structural features common to neurotransmitter-gated ion channels. Expression from cloned cDNAs of the epsilon 1 subunit together with the zeta 1 subunit in Xenopus oocytes yields functional GluR channels with high activity and characteristics of the NMDA Receptor channel. Furthermore, the heteromeric NMDA Receptor channel can be activated by glycine alone.

P Popik - One of the best experts on this subject based on the ideXlab platform.

  • The effects of NMDA Receptor antagonists on acute morphine antinociception in mice.
    Amino Acids, 2002
    Co-Authors: E Kozela, P Popik
    Abstract:

    Antagonists of the N-methyl- d-aspartate (NMDA) Receptor complex inhibit the development of tolerance to antinociceptive effects of morphine and upon acute administration, influence morphine antinociceptive activity. The analysis of numerous studies investigating acute interaction between NMDA Receptor antagonists and morphine in mice indicate a variety of procedural differences and reveal that these compounds may potentiate, attenuate and produce no effect on morphine antinociception. The conditions responsible for such conflicting experimental outcome of acute interaction remain unclear. It appears that the effects of NMDA Receptor antagonists on morphine tolerance are not causally related to their acute effects on morphine antinociception.