Deciphering the role of Gi2 in opioid-induced adenylyl cyclase supersensitization.
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.
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P H
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Department of Biochemistry and the Biotechnology Research Institute, Hong Kong University of Science and Technology, Kowloon, China.
Wong
Y H
YH
D037361:Adenylate Cyclase Toxin; D000262:Adenylyl Cyclases / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002460:Cell Line / Q000187:drug effects* / Q000378:metabolism; D005576:Colforsin / Q000378:metabolism / Q000494:pharmacology; D051960:GTP-Binding Protein alpha Subunit, Gi2; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000187:drug effects* / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D009294:Narcotics / Q000009:adverse effects*; D009293:Opioid-Related Disorders / Q000378:metabolism* / Q000503:physiopathology; D037342:Pertussis Toxin; D010766:Phosphorylation / Q000187:drug effects; D011518:Proto-Oncogene Proteins / Q000187:drug effects* / Q000378:metabolism; D011957:Receptors, Opioid / Q000187:drug effects* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects* / Q000502:physiology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D009294:Narcotics; D011518:Proto-Oncogene Proteins; D011957:Receptors, Opioid; D011993:Recombinant Fusion Proteins; D010566:Virulence Factors, Bordetella; D005576:Colforsin; D037342:Pertussis Toxin; D020928:Mitogen-Activated Protein Kinases; D051960:GTP-Binding Protein alpha Subunit, Gi2; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D000262:Adenylyl Cyclases