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Deciphering the role of Gi2 in opioid-induced adenylyl cyclase supersensitization.
- Source :
-
Neuroreport [Neuroreport] 2000 Sep 28; Vol. 11 (14), pp. 3213-7. - Publication Year :
- 2000
-
Abstract
- Prolonged opioid treatment of HEK 293 cells expressing opioid receptors are known to induce adenylyl cyclase supersensitization, a process that requires pertussis toxin (PTX)-sensitive G(i/o) proteins. Here, the role of Gi2 in adenylyl cyclase supersensitization was investigated. A PTX-insensitive G alpha(i2)/z chimera was stably co-expressed with mu-, kappa- or delta-opioid receptors in HEK 293 cells. Functional coupling of G alpha(i2)/z to the opioid receptors was demonstrated by opioid-induced inhibition of adenylyl cyclase and stimulation of ERK1/2 phosphorylation in PTX-treated cells. Chronic opioid treatment of each cell line led to adenylyl cyclase supersensitization but this response was blocked by PTX. Our results demonstrated that although PTX-sensitive G proteins are obligatory for opioid-induced adenylyl cyclase supersensitization, Gi2 alone was insufficient to mediate this response.
- Subjects :
- Adenylate Cyclase Toxin
Adenylyl Cyclases metabolism
Animals
Cell Line metabolism
Colforsin metabolism
Colforsin pharmacology
GTP-Binding Protein alpha Subunit, Gi2
GTP-Binding Protein alpha Subunits, Gi-Go metabolism
Mitogen-Activated Protein Kinases drug effects
Mitogen-Activated Protein Kinases metabolism
Opioid-Related Disorders physiopathology
Pertussis Toxin
Phosphorylation drug effects
Proto-Oncogene Proteins metabolism
Receptors, Opioid metabolism
Recombinant Fusion Proteins drug effects
Recombinant Fusion Proteins metabolism
Signal Transduction drug effects
Signal Transduction physiology
Up-Regulation physiology
Virulence Factors, Bordetella pharmacology
Adenylyl Cyclases drug effects
Cell Line drug effects
GTP-Binding Protein alpha Subunits, Gi-Go drug effects
Narcotics adverse effects
Opioid-Related Disorders metabolism
Proto-Oncogene Proteins drug effects
Receptors, Opioid drug effects
Up-Regulation drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 0959-4965
- Volume :
- 11
- Issue :
- 14
- Database :
- MEDLINE
- Journal :
- Neuroreport
- Publication Type :
- Academic Journal
- Accession number :
- 11043551
- Full Text :
- https://doi.org/10.1097/00001756-200009280-00033