| pubmed-article:18955034 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:18955034 | lifeskim:mentions | umls-concept:C0087111 | lld:lifeskim |
| pubmed-article:18955034 | lifeskim:mentions | umls-concept:C0012010 | lld:lifeskim |
| pubmed-article:18955034 | lifeskim:mentions | umls-concept:C0205245 | lld:lifeskim |
| pubmed-article:18955034 | lifeskim:mentions | umls-concept:C2825032 | lld:lifeskim |
| pubmed-article:18955034 | lifeskim:mentions | umls-concept:C1280500 | lld:lifeskim |
| pubmed-article:18955034 | lifeskim:mentions | umls-concept:C0443199 | lld:lifeskim |
| pubmed-article:18955034 | lifeskim:mentions | umls-concept:C0597360 | lld:lifeskim |
| pubmed-article:18955034 | lifeskim:mentions | umls-concept:C1948027 | lld:lifeskim |
| pubmed-article:18955034 | pubmed:dateCreated | 2008-12-16 | lld:pubmed |
| pubmed-article:18955034 | pubmed:abstractText | Prolonged exposure to benzodiazepines, drugs known to produce tolerance and dependence and also to be abused, leads to adaptive changes in GABA(A) receptors. To further explore the mechanisms responsible for these phenomena, we studied the effects of prolonged diazepam treatment on the recombinant alpha(1)beta(2)gamma(2S) GABA(A) receptors, stably expressed in human embryonic kidney (HEK) 293 cells. The results demonstrating that long-term (48 and 72 h) exposure of cells to a high concentration of diazepam (50 microM) enhanced the maximum number (B(max)) of [(3)H]flunitrazepam, [(3)H]muscimol and [(3)H]t-butylbicycloorthobenzoate ([(3)H]TBOB) binding sites, without changing their affinity (K(d)), suggested the up-regulation of GABA(A) receptors. As demonstrated by cell counting and WST-1 proliferation assay, the observed increase in receptor expression was not a consequence of stimulated growth of cells exposed to diazepam. Semi-quantitative RT-PCR and Western blot analysis, showing elevated levels of alpha(1) subunit mRNA as well as beta(2) and gamma(2) subunit proteins, respectively, suggested that prolonged high dose diazepam treatment induced de novo receptor synthesis by acting at both transcriptional and translational levels. The finding that the number of GABA(A) receptor binding sites returned to control value 24 h following diazepam withdrawal, makes this process less likely to account for the development of benzodiazepine tolerance and dependence. On the other hand, the results demonstrating that observed functional uncoupling between GABA and benzodiazepine binding sites persisted after the termination of diazepam treatment supported the hypothesis of its possible role in these phenomena. | lld:pubmed |
| pubmed-article:18955034 | pubmed:language | eng | lld:pubmed |
| pubmed-article:18955034 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18955034 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:18955034 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18955034 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18955034 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:18955034 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18955034 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18955034 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18955034 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18955034 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18955034 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18955034 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:18955034 | pubmed:month | Dec | lld:pubmed |
| pubmed-article:18955034 | pubmed:issn | 1872-6240 | lld:pubmed |
| pubmed-article:18955034 | pubmed:author | pubmed-author:Perici?DankaD | lld:pubmed |
| pubmed-article:18955034 | pubmed:author | pubmed-author:Jazvins?ak... | lld:pubmed |
| pubmed-article:18955034 | pubmed:author | pubmed-author:Svob... | lld:pubmed |
| pubmed-article:18955034 | pubmed:author | pubmed-author:Vlaini?Josipa... | lld:pubmed |
| pubmed-article:18955034 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:18955034 | pubmed:day | 30 | lld:pubmed |
| pubmed-article:18955034 | pubmed:volume | 1246 | lld:pubmed |
| pubmed-article:18955034 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:18955034 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:18955034 | pubmed:pagination | 29-40 | lld:pubmed |
| pubmed-article:18955034 | pubmed:dateRevised | 2010-11-18 | lld:pubmed |
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| pubmed-article:18955034 | pubmed:meshHeading | pubmed-meshheading:18955034... | lld:pubmed |
| pubmed-article:18955034 | pubmed:year | 2008 | lld:pubmed |
| pubmed-article:18955034 | pubmed:articleTitle | Differential effects of diazepam treatment and withdrawal on recombinant GABAA receptor expression and functional coupling. | lld:pubmed |
| pubmed-article:18955034 | pubmed:affiliation | Ruder Boskovi? Institute, Laboratory for Molecular Neuropharmacology, Division of Molecular Medicine, P.O.B. 180, 10002 Zagreb, Croatia. dsvob@irb.hr | lld:pubmed |
| pubmed-article:18955034 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:18955034 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:18955034 | lld:pubmed |
