期刊
PHARMACOLOGY
卷 82, 期 4, 页码 257-263出版社
KARGER
DOI: 10.1159/000161063
关键词
P2Y(1) receptor; Astrocyte; Dorsal spinal cord; Glutamate; Inorganic Ca(2+) concentration; MRS2179
资金
- National Natural Science Foundation of China [30470557, 30672022]
It was reported that ATP, an excitatory chemical mediator, exerts its effects by activation of the P2X (ligand-gated cationic channels) and P2Y (G protein-coupled receptors) purinoceptors in the nervous system. In the present work, we used confocal laser scanning microscopy and high-performance liquid chromatography to assess the role of the P2Y 1 receptor in ATP-evoked Ca(2+) mobilization and glutamate release from cultured dorsal spinal cord astrocytes. ATP (0.01-100 mu mol/l) produces a dose-dependent rise in the Ca(2+) relative fluorescence intensity in cultured astrocytes. N6-methyl-2'-deoxyadenosine-3',5'-bisphosphate (MRS2179, 0.01-100 mu mol/l), a P2Y(1)-specific antagonist, could dose-dependently inhibit ATP-evoked Ca(2+) mobilization. In addition, 100 mu mol/l ATP caused glutamate efflux from cultured dorsal spinal cord astrocytes in a time-dependent manner. 100 mu mol/l MRS2179 significantly inhibited the glutamate efflux induced by ATP, which suggests that P2Y(1) receptor activation is responsible for the ATP-induced glutamate efflux from astrocytes. Taken together, our results demonstrate that P2Y(1) receptor plays an important role in modulating the function of astrocytes, which raises the possibility that MRS2179, a potent P2Y(1)-specific antagonist, may become a potential drug in treating many chronic neurological diseases characterized by astrocytic activation in the nervous system. Copyright (C) 2008 S. Karger AG, Basel.
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