Source:http://linkedlifedata.com/resource/pubmed/id/12421353
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4
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| pubmed:dateCreated |
2002-11-7
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| pubmed:abstractText |
To determine the intracellular signal transduction pathway responsible for the development of tolerance/dependence, the ability of Gzalpha to substitute for pertussis toxin (PTX)-sensitive G proteins in mediating adenylyl cyclase (AC) supersensitivity was examined in the presence of defined AC isoforms. In transiently micro-opioid receptor (OR) transfected COS-7 cells (endogenous inhibitory G proteins: Gialpha2, Gialpha3 and Gzalpha), neither acute (1 micro mol/L) nor chronic morphine treatment (1 micromol/L; 18 h) influenced intracellular cAMP production. Coexpression of the micro -OR together with AC type V and VI fully restored the ability of morphine to acutely inhibit cAMP generation. Chronic morphine treatment further resulted in the development of tolerance/dependence, as assessed by desensitization of the acute inhibitory opioid effect (tolerance) as well as the induction of AC supersensitivity after drug withdrawal (dependence). Specific direction of micro -OR signalling via Gzalpha by both PTX treatment and Gzalpha over-expression had no effect on chronic morphine regulation of AC type V, but completely abolished the development of tolerance/dependence with AC type VI. Similar results were obtained in stably micro -OR-expressing HEK293 cells transiently cotransfected with Gzalpha and either AC type V or VI. Coprecipitation studies further verified that Gzalpha specifically binds to AC type V but not type VI. Taken together, these results demonstrate that in principle each of the OR-activated G proteins per se is able to mediate AC supersensitivity. However, they also indicate that it is the molecular nature of AC isoform that selects and determines the OR-activated G protein mediating tolerance/dependence.
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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/Adenylate Cyclase,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/Forskolin,
http://linkedlifedata.com/resource/pubmed/chemical/GNAZ protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Protein alpha Subunits,
http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Heterotrimeric GTP-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Morphine,
http://linkedlifedata.com/resource/pubmed/chemical/Narcotics,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Opioid, mu,
http://linkedlifedata.com/resource/pubmed/chemical/adenylyl cyclase 6,
http://linkedlifedata.com/resource/pubmed/chemical/adenylyl cyclase type V
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| pubmed:status |
MEDLINE
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| pubmed:month |
Nov
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| pubmed:issn |
0022-3042
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
83
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
818-27
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| pubmed:dateRevised |
2010-10-13
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| pubmed:meshHeading |
pubmed-meshheading:12421353-Adenylate Cyclase,
pubmed-meshheading:12421353-Animals,
pubmed-meshheading:12421353-COS Cells,
pubmed-meshheading:12421353-Cyclic AMP,
pubmed-meshheading:12421353-Dose-Response Relationship, Drug,
pubmed-meshheading:12421353-Drug Tolerance,
pubmed-meshheading:12421353-Enzyme Activation,
pubmed-meshheading:12421353-Forskolin,
pubmed-meshheading:12421353-GTP-Binding Protein alpha Subunits,
pubmed-meshheading:12421353-GTP-Binding Proteins,
pubmed-meshheading:12421353-Heterotrimeric GTP-Binding Proteins,
pubmed-meshheading:12421353-Humans,
pubmed-meshheading:12421353-Isoenzymes,
pubmed-meshheading:12421353-Kidney,
pubmed-meshheading:12421353-Morphine,
pubmed-meshheading:12421353-Narcotics,
pubmed-meshheading:12421353-Protein Binding,
pubmed-meshheading:12421353-Receptors, Opioid, mu,
pubmed-meshheading:12421353-Signal Transduction,
pubmed-meshheading:12421353-Substance-Related Disorders,
pubmed-meshheading:12421353-Time,
pubmed-meshheading:12421353-Transfection
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| pubmed:year |
2002
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| pubmed:articleTitle |
Identity of adenylyl cyclase isoform determines the G protein mediating chronic opioid-induced adenylyl cyclase supersensitivity.
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| pubmed:affiliation |
Institute of Pharmacology, Toxicology and Pharmacy, University of Munich, Munich, Germany. ammer@pharmtox.vetmed.uni-muenchen.de
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| pubmed:publicationType |
Journal Article
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