| Bromocriptine, an ergot alkaloid, inhibits excitatory amino acid release mediated by glutamate transporter reversal. | |
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MedLine Citation:
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PMID: 20599932 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Bromocriptine, a dopamine D(2) receptor agonist, has widely been used for patients with Parkinson's disease. The aim of the present study was to investigate the effect of bromocriptine on glutamate transporter. Since the astroglial glutamate transporter GLT-1 (EAAT2) is the predominant isoform in the forebrain, we generated EAAT2-expressing human embryonic kidney cells and immortalized mouse astrocytes. In the present studies, we observed a GLT-1-immunoreactive band and significant Na(+)-dependent d-[(3)H] aspartate uptake. Furthermore, the glutamate transporter inhibitors, dl-threo-beta-benzyloxyaspartic acid (TBOA) and dihydrokainate (DHK), displayed a dose-dependent reduction of d-[(3)H] aspartate uptake in both types of cells. In contrast, cells exposed to either chemical anoxia or high KCl elicited a marked release of d-[(3)H] aspartate, and the release was inhibited by TBOA and DHK, implying the contribution of glutamate transporter reversal. Interestingly, we found that bromocriptine dose-dependently inhibits d-[(3)H] aspartate release elicited by chemical anoxia or high KCl, while no changes occurred in the uptake. The inhibitory action of bromocriptine was not affected by sulpiride, a dopamine D(2) receptor antagonist. On the other hand, bromocriptine had no effect on swelling-induced d-[(3)H] aspartate release, which is mediated by volume-regulated anion channels. In vivo studies revealed that bromocriptine suppresses the excessive elevation of glutamate levels in gerbils subjected to transient forebrain ischemia in a manner similar to DHK. Taken together, these results provide evidence that bromocriptine inhibits excitatory amino acid release via reversed operation of GLT-1 without altering forward transport. |
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Authors:
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Yasufumi Shirasaki; Masunobu Sugimura; Toshiyuki Sato |
Publication Detail:
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Type: Journal Article Date: 2010-06-21 |
Journal Detail:
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Title: European journal of pharmacology Volume: 643 ISSN: 1879-0712 ISO Abbreviation: Eur. J. Pharmacol. Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-07-26 Completed Date: 2010-12-07 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 1254354 Medline TA: Eur J Pharmacol Country: Netherlands |
Other Details:
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Languages: eng Pagination: 48-57 Citation Subset: IM |
Copyright Information:
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Copyright (c) 2010 Elsevier B.V. All rights reserved. |
Affiliation:
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Biological Research Laboratories, Daiichi-Sankyo Co., Ltd., Tokyo, Japan. shirasaki.yasufumi.n7@daiichisankyo.co.jp |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Astrocytes / drug effects*, metabolism Blotting, Western Bromocriptine / pharmacology* Cell Line Dopamine Agonists / pharmacology* Dose-Response Relationship, Drug Excitatory Amino Acid Antagonists / pharmacology* Excitatory Amino Acid Transporter 2 / metabolism* Excitatory Amino Acids / antagonists & inhibitors* Glutamic Acid / metabolism Humans Mice Transfection |
| Chemical | |
Reg. No./Substance:
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0/Dopamine Agonists; 0/Excitatory Amino Acid Antagonists; 0/Excitatory Amino Acid Transporter 2; 0/Excitatory Amino Acids; 25614-03-3/Bromocriptine; 56-86-0/Glutamic Acid |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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