Source:http://linkedlifedata.com/resource/pubmed/id/12653973
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
5
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| pubmed:dateCreated |
2003-3-25
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| pubmed:abstractText |
The present study explored a possible role for RGS (regulators of G protein signalling) proteins in the long term actions of morphine in the locus coeruleus (LC), a brainstem region implicated in opiate physical dependence and withdrawal. Morphine influences LC neurons through activation of micro -opioid receptors, which, being Gi/o-linked, would be expected to be modulated by RGS proteins. We focused on several RGS subtypes that are known to be expressed in this brain region. Levels of mRNAs encoding RGS2, -3, -4, -5, -7, -8 and -11 are unchanged following chronic morphine, but RGS2 and -4 mRNA levels are increased 2-3-fold 6 h following precipitation of opiate withdrawal. The increases in RGS2 and -4 mRNA peak after 6 h of withdrawal and return to control levels by 24 h. Immunoblot analysis of RGS4 revealed a striking divergence between mRNA and protein responses in LC: protein levels are elevated twofold following chronic morphine and decrease to control values by 6 h of withdrawal. In contrast, levels of RGS7 and -11 proteins, the only other subtypes for which antibodies are available, were not altered by these treatments. Intracellular application of wild-type RGS4, but not a GTPase accelerating-deficient mutant of RGS4, into LC neurons diminished electrophysiological responses to morphine. The observed subtype- and time-specific regulation of RGS4 protein and mRNA, and the diminished morphine-induced currents in the presence of elevated RGS4 protein levels, indicate that morphine induction of RGS4 could contribute to aspects of opiate tolerance and dependence displayed by LC neurons.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Morphine,
http://linkedlifedata.com/resource/pubmed/chemical/Naltrexone,
http://linkedlifedata.com/resource/pubmed/chemical/Narcotic Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Narcotics,
http://linkedlifedata.com/resource/pubmed/chemical/RGS Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/RGS4 protein,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger
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| pubmed:status |
MEDLINE
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| pubmed:month |
Mar
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| pubmed:issn |
0953-816X
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
17
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
971-80
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| pubmed:dateRevised |
2006-11-15
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| pubmed:meshHeading |
pubmed-meshheading:12653973-Animals,
pubmed-meshheading:12653973-Blotting, Western,
pubmed-meshheading:12653973-Immunohistochemistry,
pubmed-meshheading:12653973-In Situ Hybridization,
pubmed-meshheading:12653973-Locus Coeruleus,
pubmed-meshheading:12653973-Male,
pubmed-meshheading:12653973-Membrane Potentials,
pubmed-meshheading:12653973-Morphine,
pubmed-meshheading:12653973-Naltrexone,
pubmed-meshheading:12653973-Narcotic Antagonists,
pubmed-meshheading:12653973-Narcotics,
pubmed-meshheading:12653973-Neurons,
pubmed-meshheading:12653973-Organ Culture Techniques,
pubmed-meshheading:12653973-Patch-Clamp Techniques,
pubmed-meshheading:12653973-RGS Proteins,
pubmed-meshheading:12653973-RNA, Messenger,
pubmed-meshheading:12653973-Rats,
pubmed-meshheading:12653973-Rats, Sprague-Dawley,
pubmed-meshheading:12653973-Substance Withdrawal Syndrome
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| pubmed:year |
2003
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| pubmed:articleTitle |
Regulation of RGS proteins by chronic morphine in rat locus coeruleus.
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| pubmed:affiliation |
Department of Psychiatry, The University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd, Dallas TX 75390, USA. stephen.gold@utsouthwestern.edu
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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