12654503

Source:http://linkedlifedata.com/resource/pubmed/id/12654503

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Predicate	Object
rdf:type	pubmed:Citation
lifeskim:mentions	umls-concept:C0003289, umls-concept:C0033684, umls-concept:C0162783, umls-concept:C0332281, umls-concept:C0681850, umls-concept:C0851285, umls-concept:C0872383, umls-concept:C1269683, umls-concept:C1550501, umls-concept:C1706203, umls-concept:C2349001, umls-concept:C2697811
pubmed:issue	1-2
pubmed:dateCreated	2003-3-25
pubmed:abstractText	G protein-coupled receptor kinases (GRKs) and beta-arrestin-2 play a crucial role in the regulation of neurotransmitter receptors in brain. In this study, GRK 2, GRK 6, beta-arrestin-2 and associated proteins (Gbeta proteins and protein phosphatase (PP)-2A) were quantitated in parallel (immunodensity with specific antibodies) in brains of depressed subjects (drug-free and antidepressant-treated) to investigate the effect of major depression and antidepressant drugs on these receptor regulatory proteins. Specimens of the prefrontal cortex (Brodmann's area 9) were collected from 19 suicide and non-suicide depressed subjects and 13 control subjects. In drug-free (n=9), but not in antidepressant-treated (n=10), depressed subjects an increase in the density of membrane-associated GRK 2 (30%, n=9, P=0.005) was found compared with that in sex-, age-, and PMD-matched controls. Comparison between drug-free and antidepressant-treated depressed subjects showed that GRK 2 was reduced in membrane (39%, n=10, P=0.008) and cytosolic (44%, n=10, P=0.09) preparations after antidepressant drug treatment. In contrast, membrane-associated GRK 6 (drug-free and antidepressant-treated depressed subjects) was found unchanged when compared with that in matched controls. Similarly, the densities of beta-arrestin-2, PP-2A, and Gbeta proteins were not significantly different from those in matched controls. There was a positive correlation between the immunodensities of GRK 2 and beta-arrestin-2 in membrane preparations (r=0.48, n=19, P=0.04), suggesting that both proteins are regulated in a coordinated manner in brains of depressed subjects. The results of this study indicate that major depression is associated with upregulation of brain GRK 2, but not GRK 6, and that antidepressant drug treatment appears to induce downregulation of GRK 2 protein.
pubmed:language	eng
pubmed:journal	http://linkedlifedata.com/resource/pubmed/journal/8908640
pubmed:citationSubset	IM
pubmed:chemical	http://linkedlifedata.com/resource/pubmed/chemical/Antidepressive Agents, http://linkedlifedata.com/resource/pubmed/chemical/Arrestins, http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP-Dependent Protein Kinases, http://linkedlifedata.com/resource/pubmed/chemical/G-Protein-Coupled Receptor Kinases, http://linkedlifedata.com/resource/pubmed/chemical/G-protein-coupled receptor kinase 6, http://linkedlifedata.com/resource/pubmed/chemical/Heterotrimeric GTP-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Phosphoprotein Phosphatases, http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Neurotransmitter, http://linkedlifedata.com/resource/pubmed/chemical/beta-Adrenergic Receptor Kinases, http://linkedlifedata.com/resource/pubmed/chemical/beta-arrestin
pubmed:status	MEDLINE
pubmed:month	Mar
pubmed:issn	0169-328X
pubmed:author	pubmed-author:Ferrer-AlcónMarcelM, pubmed-author:García-SevillaJesús AJA, pubmed-author:Grange-MidroitMurielM, pubmed-author:GuimónJoséJ, pubmed-author:HugueletPhilippeP, pubmed-author:La HarpeRomanoR
pubmed:issnType	Print
pubmed:day	17
pubmed:volume	111
pubmed:owner	NLM
pubmed:authorsComplete	Y
pubmed:pagination	31-41
pubmed:dateRevised	2009-11-19
pubmed:meshHeading	pubmed-meshheading:12654503-Adult, pubmed-meshheading:12654503-Aged, pubmed-meshheading:12654503-Antidepressive Agents, pubmed-meshheading:12654503-Arrestins, pubmed-meshheading:12654503-Cell Membrane, pubmed-meshheading:12654503-Cyclic AMP-Dependent Protein Kinases, pubmed-meshheading:12654503-Depressive Disorder, Major, pubmed-meshheading:12654503-Down-Regulation, pubmed-meshheading:12654503-Female, pubmed-meshheading:12654503-G-Protein-Coupled Receptor Kinases, pubmed-meshheading:12654503-Heterotrimeric GTP-Binding Proteins, pubmed-meshheading:12654503-Humans, pubmed-meshheading:12654503-Immunohistochemistry, pubmed-meshheading:12654503-Male, pubmed-meshheading:12654503-Middle Aged, pubmed-meshheading:12654503-Phosphoprotein Phosphatases, pubmed-meshheading:12654503-Prefrontal Cortex, pubmed-meshheading:12654503-Protein-Serine-Threonine Kinases, pubmed-meshheading:12654503-Receptors, Neurotransmitter, pubmed-meshheading:12654503-Up-Regulation, pubmed-meshheading:12654503-beta-Adrenergic Receptor Kinases
pubmed:year	2003
pubmed:articleTitle	Regulation of GRK 2 and 6, beta-arrestin-2 and associated proteins in the prefrontal cortex of drug-free and antidepressant drug-treated subjects with major depression.
pubmed:affiliation	Clinical Research Unit, Department of Psychiatry, University of Geneva, H.U.G., Belle-Idée (Les Voirons), CH-1225 Chêne-Bourg, Geneva, Switzerland.
pubmed:publicationType	Journal Article, Research Support, Non-U.S. Gov't