Opioid-induced adenylyl cyclase supersensitization in human embryonic kidney 293 cells requires pertussis toxin-sensitive G proteins other than G i1 and G i3

Abstract

Chronic activation of opioid receptors in cultured mammalian cells is known to induce adenylyl cyclase (AC) supersensitization via the pertussis toxin-sensitive G i/o proteins. To examine the role of G i1 and G i3 in opioid-induced AC supersensitization, pertussis toxin-resistant mutants of Gα i1 and Gα i3 (Gα i1CG and Gα i3CG) were stably co-expressed with different opioid receptors (μ, δ or κ) in human embryonic kidney (HEK 293) cells. Although the opioid receptors were capable of inhibiting AC via Gα i1CG and Gα i3CG in pertussis toxin-treated cells, AC supersensitization induced by chronic opioid treatment remained sensitive to pertussis toxin. Our results demonstrated that despite their ability to interact with opioid receptors, the pertussis toxin-sensitive G i1 and G i3 proteins on their own are incapable of supporting opioid-induced AC supersensitization.