%0 Journal Article %A Prudence H. Tso %A Yung H. Wong %T Gz Can Mediate the Acute Actions of μ- and κ-Opioids but Is Not Involved in Opioid-Induced Adenylyl Cyclase Supersensitization %D 2000 %J Journal of Pharmacology and Experimental Therapeutics %P 168-176 %V 295 %N 1 %X The three subtypes of opioid receptors (δ, μ, and κ) are known to regulate multiple effectors through either pertussis toxin-sensitive or -insensitive G proteins. In opioid-induced inhibition of adenylyl cyclase, both Gi and Gz proteins can serve as the signal transducer. Our previous study showed that opioid-induced adenylyl cyclase supersensitization in human embryonic kidney (HEK) 293 cells expressing the δ-opioid receptor requires Gi but not Gz proteins. Herein, we studied the ability of μ- and κ-opioid receptors to regulate the activities of adenylyl cyclase through Gz. In HEK 293 cells coexpressing Gzwith the μ- or κ-opioid receptors, opioid agonists induced inhibition of adenylyl cyclase in a pertussis toxin-insensitive manner. However, adenylyl cyclase supersensitization induced by chronic opioid treatments remained sensitive to pertussis toxin. We also showed that the responsiveness of cAMP-dependent response element-binding proteins to forskolin was not altered after prolonged opioid treatment but was higher in cells coexpressing Gz. Although the μ- and κ-opioid receptors mediated acute activation of extracellular signal-regulated protein kinase 1/2 via both Gi and Gz, these responses were abolished by chronic opioid treatment. These studies showed that Gzcould mediate acute actions of μ- and κ-opioids but Gzalone was insufficient to mediate adenylyl cyclase supersensitization induced by the chronic activation of opioid receptors. The American Society for Pharmacology and Experimental Therapeutics %U https://jpet.aspetjournals.org/content/jpet/295/1/168.full.pdf