| Cell cycle-dependent regulation of kainate-induced inward currents in microglia. | |
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MedLine Citation:
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PMID: 16962563 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Microglia are reported to have alpha-amino-hydroxy-5-methyl-isoxazole-4-propionate/kainate (KA) types. However, only small population of primary cultured rat microglia (approximately 20%) responded to KA. In the present study, we have attempted to elucidate the regulatory mechanism of responsiveness to KA in GMIR1 rat microglial cell line. When the GMIR1 cells were plated at a low density in the presence of granulocyte macrophage colony-stimulating factor, the proliferation rate increased and reached the peak after 2 days in culture and then gradually decreased because of density-dependent inhibition. At cell proliferation stage, approximately 80% of the GMIR1 cells exhibited glutamate (Glu)- and KA-induced inward currents at cell proliferation stage, whereas only 22.5% of the cells showed responsiveness to Glu and KA at cell quiescent stage. Furthermore, the mean amplitudes of inward currents induced by Glu and KA at cell proliferation stage (13.8+/-3.0 and 8.4+/-0.6 pA) were significantly larger than those obtained at cell quiescent stage (4.7+/-0.8 and 6.2+/-1.2 pA). In the GMIR1 cells, KA-induced inward currents were markedly inhibited by (RS)-3-(2-carboxybenzyl) willardiine (UBP296), a selective antagonist for KA receptors. The KA-responsive cells also responded to (RS)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl) propanoic acid (ATPA), a selective agonist for GluR5, in both GMIR1 cells and primary cultured rat microglia. Furthermore, mRNA levels of the KA receptor subunits, GluR5 and GluR6, at the cell proliferation stage were significantly higher than those at the cell quiescent stage. Furthermore, the immunoreactivity for GluR6/7 was found to increase in activated microglia in the post-ischemic hippocampus. These results strongly suggest that microglia have functional KA receptors mainly consisting of GluR5 and GluR6, and the expression levels of these subunits are closely regulated by the cell cycle mechanism. |
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Authors:
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Jun Yamada; Makoto Sawada; Hiroshi Nakanishi |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2006-08-31 |
Journal Detail:
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Title: Biochemical and biophysical research communications Volume: 349 ISSN: 0006-291X ISO Abbreviation: Biochem. Biophys. Res. Commun. Publication Date: 2006 Oct |
Date Detail:
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Created Date: 2006-09-22 Completed Date: 2006-11-07 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0372516 Medline TA: Biochem Biophys Res Commun Country: United States |
Other Details:
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Languages: eng Pagination: 913-9 Citation Subset: IM |
Affiliation:
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Laboratory of Oral Aging Science, Faculty of Dental Sciences, Kyushu University, Fukuoka 812-8582, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Count Cell Cycle* Cell Line Down-Regulation Electrophysiology Glutamic Acid / pharmacology Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology Kainic Acid / pharmacology* Microglia / cytology*, drug effects* Patch-Clamp Techniques Rats Receptors, Kainic Acid / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Receptors, Kainic Acid; 487-79-6/Kainic Acid; 56-86-0/Glutamic Acid; 83869-56-1/Granulocyte-Macrophage Colony-Stimulating Factor |
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