Deciphering the role of G(i2) 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 requir es pertussis toxin (PTX)-sensitive G(i/o) proteins. Here, the role of G(i2) in adenylyl cyclase supersensitization was investigated. A PTX-insensitive G alpha(i2)/z chimera was stably co-expressed with mu-, kappa- or delta-op ioid receptores in HEK 293 cells. Functional coupling fo G alpha(i2)/z to t he opioid receptors was demonstrated by opioid-induced inhibition of adenyl yl cyclase and stimulation of ERK1/2 phosphorylation in PTX-treated cells. Chronic opioid treatment of each cell line led to adenylyl cyclase supersen sitization but this response was blocked by PTX. Our results demonstrated t hat although PTX-sensitive G proteins are obligatory for opioid-induced ade nylyl cyclase supersensitization, G(i2) alone was insufficient to mediate t his response. NeuroReport 11:3213-3217 (C) 2000 Lippincott Williams & Wilki ns.