Group Ⅱ and Ⅲ metabotropic glutamate receptors agonists reverse 1-methyl-4-phenylpyridinium-induced glutamate uptake inhibition

Abstract

Abstract: AIM: To study the effects of group Ⅱ and Ⅲ metabotropic glutamate receptors (mGluRs) agonists on 1-methyl-4-phenylpyridinium (MPP +)-induced glutamate uptake inhibition. METHODS: The glutamate uptake into astrocytes was measured by using radio-ligand binding assay method, and the viability of astrocytes was investigated by MTT method. RESULTS: It was shown that MPP + (150, 200 μmol·L^-1) inhibited glutamate uptake into astrocytes, but produced no effect on the viability of astrocytes, and the inhibition rates were 58.3 % and 70.1 %, respectively.Group Ⅱ mGluRs agonist (2' S, 2' R, 3' R)-2-(2', 3'-dicarboxycyclopropyl) glycine (DCG-IV) (0.1, 1, 10, 100 μmol·L^-1) and Group Ⅲ mGluRs agonist L (+)-2-amino-4-phosphonobutyric acid (L-AP4) (1, 10, 100 μmol·L^-1) significantly reversed MPP +-induced glutamate uptake inhibition. CONCLUSION: MPP + directly inhibits the function of glutamate transporters, and group Ⅱ and Ⅲ mGluRs agonists produce neuroprotective effects by enhancing the activity of glutamate transporters.

Key words: metabotropic glutamate receptors, 1-methyl-4-phenylpyridinium, astrocytes, glutamate uptake

CLC Number:

WANG Fang, YAO Hong-Hong, HU Gang. Group Ⅱ and Ⅲ metabotropic glutamate receptors agonists reverse 1-methyl-4-phenylpyridinium-induced glutamate uptake inhibition[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2004, 9(5): 485-489.

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