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Opposite effects of Zn on the in vitro binding of [ 3 H]LY354740 to recombinant and native metabotropic glutamate 2 and 3 receptors
Author(s) -
Malherbe Pari,
Richards J. Grayson,
Broger Clemens,
Zenner MarieThérèse,
Messer Jürg,
Kratzeisen Claudia,
Nakanishi Shigetada,
Mutel Vincent
Publication year - 2005
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2005.03176.x
Subject(s) - metabotropic glutamate receptor , metabotropic receptor , recombinant dna , glutamate receptor , metabotropic glutamate receptor 5 , metabotropic glutamate receptor 1 , metabotropic glutamate receptor 4 , chemistry , receptor , neuroscience , in vitro , metabotropic glutamate receptor 2 , pharmacology , biochemistry , biology , gene
We investigated the effect of Zn on agonist binding to both recombinant and native mGlu2 and mGlu3 receptors. Zn had a biphasic inhibitory effect on recombinant mGlu2 with IC 50 values for the high‐ and low‐affinity components of 60 ± 10 µ m and 2 ± 0.7 m m , respectively. Zn induced a complex biphasic effect of inhibition and enhancement of [ 3 H]LY354740 binding to mGlu3. Observations with a series of chimeric mGlu2/3 receptors suggest that the Zn effect resides in the N‐terminal domain of mGlu2 and mGlu3. We observed that the His56 of mGlu2, which corresponds to Asp63 in mGlu3 was largely accountable for the second phase of the Zn effect. As revealed by quantitative receptor radioautography, the addition of up to 100 µ m Zn to brain sections of wild‐type mice resulted in significant decreases in binding density in most brain regions. In particular, the mid‐molecular layer of the dentate gyrus (DGmol) and the CA1 lacunosum moleculare of hippocampus (CA1‐LMol) showed reductions of 62 and 67%, respectively. In contrast, the addition of 300 µ m Zn to brain sections of mGlu2 –/– mice caused large increases in binding density of 289 and 242% in DGmol and CA1‐LMol, respectively. Therefore, Zn might play a role as a physiological modulator of group II mGlu receptor function.