Linked Life Data

18455202

Source:http://linkedlifedata.com/resource/pubmed/id/18455202

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2008-5-27
pubmed:abstractText
Drugs acting at dopamine D2-like receptors play a pivotal role in the treatment of both schizophrenia and Parkinson's disease. Recent studies have demonstrated a role for G-protein independent D2 receptor signaling pathways acting through beta-arrestin. In this study we describe the establishment of a Bioluminescence Resonance Energy Transfer (BRET) assay for measuring dopamine induced recruitment of human beta-arrestin2 to the human dopamine D2 receptor. Dopamine, as well as the dopamine receptor agonists pramipexole and quinpirole, acted as full agonists in the assay as reflected by their ability to elicit marked concentration dependent increases in the BRET signal signifying beta-arrestin2 recruitment to the D2 receptor. As expected from their effect on G-protein coupling and cAMP levels mediated through the D2 receptor RNPA, pergolide, apomorphine, ropinirole, bromocriptine, 3PPP, terguride, aripiprazole, SNPA all acted as partial agonists with decreasing efficacy in the BRET assay. In contrast, a wide selection of typical and atypical anti-psychotics was incapable of stimulating beta-arrestin2 recruitment to the D2 receptor. Moreover, we observed that haloperidol, sertindole, olanzapine, clozapine and ziprasidone all fully inhibited the dopamine induced beta-arrestin2 recruitment to D2 receptor (short variant) in a concentration dependent manner. We conclude that most anti-psychotics are incapable of stimulating beta-arrestin2 recruitment to the dopamine D2 receptor, in accordance with their antagonistic properties at the level of G-protein coupling.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0028-3908
pubmed:author
pubmed:issnType
Print
pubmed:volume
54
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1215-22
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:18455202-Amino Acid Sequence, pubmed-meshheading:18455202-Antiparkinson Agents, pubmed-meshheading:18455202-Antipsychotic Agents, pubmed-meshheading:18455202-Arrestins, pubmed-meshheading:18455202-Cells, Cultured, pubmed-meshheading:18455202-Cyclic AMP, pubmed-meshheading:18455202-DNA, pubmed-meshheading:18455202-Data Interpretation, Statistical, pubmed-meshheading:18455202-Fluorescence Resonance Energy Transfer, pubmed-meshheading:18455202-Guanosine 5'-O-(3-Thiotriphosphate), pubmed-meshheading:18455202-Humans, pubmed-meshheading:18455202-Microscopy, Confocal, pubmed-meshheading:18455202-Molecular Sequence Data, pubmed-meshheading:18455202-Pharmaceutical Vehicles, pubmed-meshheading:18455202-Plasmids, pubmed-meshheading:18455202-Receptors, Dopamine D2, pubmed-meshheading:18455202-Transfection
pubmed:year
2008
pubmed:articleTitle
Recruitment of beta-arrestin2 to the dopamine D2 receptor: insights into anti-psychotic and anti-parkinsonian drug receptor signaling.
pubmed:affiliation
H. Lundbeck A/S, Ottiliavej 9, 2500 Valby, Denmark. ibkl@sund.ku.dk
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't