Linked Life Data

20599932

Source:http://linkedlifedata.com/resource/pubmed/id/20599932

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2010-7-26
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1879-0712
pubmed:author
pubmed:copyrightInfo
Copyright (c) 2010 Elsevier B.V. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
643
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
48-57
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Bromocriptine, an ergot alkaloid, inhibits excitatory amino acid release mediated by glutamate transporter reversal.
pubmed:affiliation
Biological Research Laboratories, Daiichi-Sankyo Co., Ltd., Tokyo, Japan. shirasaki.yasufumi.n7@daiichisankyo.co.jp
pubmed:publicationType
Journal Article