Linked Life Data

17382299

Source:http://linkedlifedata.com/resource/pubmed/id/17382299

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2007-5-8
pubmed:abstractText
The effects of the antidepressant drugs clomipramine (CLOM), desipramine (DMI), tianeptine (TIAN) and of norfluoxetine (NORF, the active metabolite of fluoxetine), were investigated in CHO cells expressing human beta2 adrenoceptors and a secreted placental alkaline phosphatase (SPAP) reporter gene to determine their actions on cyclic AMP-driven gene transcription. After 18 h of exposure, CLOM, DMI and NORF, but not TIAN, had biphasic effects on 1 microM isoprenaline-stimulated SPAP fsproduction with concentrations between 10 nM and 1 microM enhancing the maximal (E(max)) SPAP response, without changing EC50 values, but higher concentrations produced marked inhibitory effects. At nanomolar concentrations, CLOM and DMI increased expression of phospho-CREB (cyclic AMP response element binding protein). NORF was less effective but did significantly increase phospho-CREB at a concentration of 200 nM. TIAN had no effect. None of the antidepressants had any effect on CREB expression, nor on the accumulation of cyclic AMP. After prolonged exposure (7-21 days) to a low concentration (200 nM) of the antidepressants, the enhanced E(max) values for SPAP production evident after 18 h were not maintained but CLOM and DMI induced a significant leftward shift in the isoprenaline EC50 after a 7-day period of treatment and this was sustained at the 21 day time point. TIAN did not produce any significant changes. The results demonstrate that, in vitro, some but not all antidepressants can modify gene transcription via monoamine and cyclic AMP-independent mechanisms. The in vivo adaptive responses to TIAN probably involve alterations in different gene sets to those affected by other antidepressants.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0006-2952
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
73
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1995-2003
pubmed:meshHeading
pubmed-meshheading:17382299-Alkaline Phosphatase, pubmed-meshheading:17382299-Animals, pubmed-meshheading:17382299-Antidepressive Agents, Tricyclic, pubmed-meshheading:17382299-Blotting, Western, pubmed-meshheading:17382299-CHO Cells, pubmed-meshheading:17382299-Clomipramine, pubmed-meshheading:17382299-Cricetinae, pubmed-meshheading:17382299-Cricetulus, pubmed-meshheading:17382299-Cyclic AMP Response Element-Binding Protein, pubmed-meshheading:17382299-Desipramine, pubmed-meshheading:17382299-Dose-Response Relationship, Drug, pubmed-meshheading:17382299-Fluoxetine, pubmed-meshheading:17382299-Genes, Reporter, pubmed-meshheading:17382299-Humans, pubmed-meshheading:17382299-Receptors, Adrenergic, beta-2, pubmed-meshheading:17382299-Thiazepines, pubmed-meshheading:17382299-Time Factors, pubmed-meshheading:17382299-Transcription, Genetic
pubmed:year
2007
pubmed:articleTitle
The effects of antidepressants on cyclic AMP-response element-driven gene transcription in a model cell system.
pubmed:affiliation
School of Biomedical Sciences, University of Nottingham Medical School, Queens Medical Centre, Nottingham NG7 2UH, United Kingdom.
pubmed:publicationType
Journal Article, Comparative Study