Linked Life Data

16336634

Source:http://linkedlifedata.com/resource/pubmed/id/16336634

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2005-12-22
pubmed:abstractText
In the striatum, stimulation of dopamine D2 receptors results in attenuation of glutamate responses. This effect is exerted in large part via negative regulation of AMPA glutamate receptors. Phosphorylation of the GluR1 subunit of the AMPA receptor has been proposed to play a critical role in the modulation of glutamate transmission, in striatal medium spiny neurons. Here, we have examined the effects of blockade of dopamine D2-like receptors on the phosphorylation of GluR1 at the cAMP-dependent protein kinase (PKA) site, Ser845, and at the protein kinase C and calcium/calmodulin-dependent protein kinase II site, Ser831. Administration of haloperidol, an antipsychotic drug with dopamine D2 receptor antagonistic properties, increases the phosphorylation of GluR1 at Ser845, without affecting phosphorylation at Ser831. The same effect is observed using eticlopride, a selective dopamine D2 receptor antagonist. In contrast, administration of the dopamine D2-like agonist, quinpirole, decreases GluR1 phosphorylation at Ser845. The increase in Ser845 phosphorylation produced by haloperidol is abolished in dopamine- and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32) knockout mice, or in mice in which the PKA phosphorylation site on DARPP-32 (i.e. Thr34) has been mutated (Thr34-->Ala mutant mice), and requires tonic activation of adenosine A2A receptors. These results demonstrate that dopamine D2 antagonists increase GluR1 phosphorylation at Ser845 by removing the inhibitory tone exerted by dopamine D2 receptors on the PKA/DARPP-32 cascade.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine A2 Receptor Antagonists, http://linkedlifedata.com/resource/pubmed/chemical/Dopamine Antagonists, http://linkedlifedata.com/resource/pubmed/chemical/Dopamine and cAMP-Regulated..., http://linkedlifedata.com/resource/pubmed/chemical/Haloperidol, http://linkedlifedata.com/resource/pubmed/chemical/Ppp1r1b protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Purines, http://linkedlifedata.com/resource/pubmed/chemical/Quinpirole, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, AMPA, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Dopamine D2, http://linkedlifedata.com/resource/pubmed/chemical/Serine, http://linkedlifedata.com/resource/pubmed/chemical/Threonine, http://linkedlifedata.com/resource/pubmed/chemical/glutamate receptor ionotropic..., http://linkedlifedata.com/resource/pubmed/chemical/istradefylline
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0022-3042
pubmed:author
pubmed:issnType
Print
pubmed:volume
96
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
482-8
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Regulation of phosphorylation of the GluR1 AMPA receptor by dopamine D2 receptors.
pubmed:affiliation
Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural