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

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 Gi, in opioid -induced AC supersensitization, pertussis toxin-resistant mutants of G alph a (i1) and G alpha (i3) (G alpha (i1) and G alpha (i3)CG) were stably co-ex pressed with different opioid receptors (mu, delta or kappa) in human embry onic kidney (HEK 293) cells. Although the opioid receptors were capable of inhibiting AC via G alpha (i3)CG and G alpha (i3)CG in pertussis toxin-trea ted cells, AC supersensitization induced by chronic opioid treatment remain ed sensitive to pertussis toxin. Our results demonstrated that despite thei r ability to interact with opioid receptors, the pertussis toxin-sensitive G(i1) and G(i3) proteins on their own are incapable of supporting opioid-in duced AC supersensitization. (C) 2001 Elsevier Science Ireland Ltd. All rig hts reserved.