Linked Life Data

20807772

Source:http://linkedlifedata.com/resource/pubmed/id/20807772

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
45
pubmed:dateCreated
2010-11-1
pubmed:abstractText
We identified that activation of the G(q)-linked dopamine D1-D2 receptor hetero-oligomer generates a PLC-dependent intracellular calcium signal. Confocal FRET between endogenous dopamine D1 and D2 receptors in striatal neurons confirmed a physical interaction between them. Pretreatment with SKF 83959, which selectively activates the D1-D2 receptor heteromer, or SKF 83822, which only activates the D1 receptor homo-oligomer, led to rapid desensitization of the D1-D2 receptor heteromer-mediated calcium signal in both heterologous cells and striatal neurons. This desensitization response was mediated through selective occupancy of the D1 receptor binding pocket. Although SKF 83822 was unable to activate the D1-D2 receptor heteromer, it still permitted desensitization of the calcium signal. This suggested that occupancy of the D1 receptor binding pocket by SKF 83822 resulted in conformational changes sufficient for desensitization without heteromer activation. Bioluminescence resonance energy transfer and co-immunoprecipitation studies indicated an agonist-induced physical association between the D1-D2 receptor heteromeric complex and GRK2. Increased expression of GRK2 led to a decrease in the calcium signal with or without prior exposure to either SKF 83959 or SKF 83822. GRK2 knockdown by siRNA led to an increase in the signal after pretreatment with either agonist. Expression of the catalytically inactive and RGS (regulator of G protein signaling)-mutated GRK2 constructs each led to a partial recovery of the GRK2-attenuated calcium signal. These results indicated that desensitization of the dopamine D1-D2 receptor heteromer-mediated signal can occur by agonist occupancy even without activation and is dually regulated by both the catalytic and RGS domains of GRK2.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/2,3,4,5-Tetrahydro-7,8-dihydroxy-1-p..., http://linkedlifedata.com/resource/pubmed/chemical/3-allyl-6-chloro-7,8-dihydroxy-1-(3-..., http://linkedlifedata.com/resource/pubmed/chemical/ADRBK1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Adrbk1 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Benzazepines, http://linkedlifedata.com/resource/pubmed/chemical/Calcium, http://linkedlifedata.com/resource/pubmed/chemical/Dopamine Agonists, http://linkedlifedata.com/resource/pubmed/chemical/G-Protein-Coupled Receptor Kinase 2, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Dopamine D1, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Dopamine D2, http://linkedlifedata.com/resource/pubmed/chemical/SK&F 83959
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1083-351X
pubmed:author
pubmed:issnType
Electronic
pubmed:day
5
pubmed:volume
285
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
35092-103
pubmed:dateRevised
2011-11-7
pubmed:meshHeading
pubmed-meshheading:20807772-2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine, pubmed-meshheading:20807772-Animals, pubmed-meshheading:20807772-Benzazepines, pubmed-meshheading:20807772-Calcium, pubmed-meshheading:20807772-Calcium Signaling, pubmed-meshheading:20807772-Cell Line, pubmed-meshheading:20807772-Dopamine Agonists, pubmed-meshheading:20807772-G-Protein-Coupled Receptor Kinase 2, pubmed-meshheading:20807772-Gene Knockdown Techniques, pubmed-meshheading:20807772-Humans, pubmed-meshheading:20807772-Mice, pubmed-meshheading:20807772-Neurons, pubmed-meshheading:20807772-Protein Multimerization, pubmed-meshheading:20807772-Protein Structure, Tertiary, pubmed-meshheading:20807772-Receptors, Dopamine D1, pubmed-meshheading:20807772-Receptors, Dopamine D2, pubmed-meshheading:20807772-Visual Cortex
pubmed:year
2010
pubmed:articleTitle
Dopamine D1-D2 receptor Heteromer-mediated calcium release is desensitized by D1 receptor occupancy with or without signal activation: dual functional regulation by G protein-coupled receptor kinase 2.
pubmed:affiliation
Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural