CHANGES IN THE ASSOCIATION OF G-PROTEIN SUBUNITS WITH THE CLONED MOUSE DELTA-OPIOID RECEPTOR ON AGONIST STIMULATION

G proteins couple delta opioid receptors to multiple cellular effector systems and are critical components of the delta opioid signal transd uction cascade. To investigate the physical association of della opioi d receptors with G proteins, the cloned mouse delta opioid receptor wa s solubilized, and the G proteins associated with the receptor were id entified through coimmunoprecipitation of the receptor/G protein compl exes with antisera directed against different G(alpha) and G(beta) sub units. The delta receptor associates with G(i alpha 1), G(i alpha 3), G(o alpha), G(beta 1) and G(beta 2) subtypes. On agonist binding to th e receptor, a greater proportion of the receptor is associated with G( i alpha) than with G(o alpha) G(i alpha 1) dissociates from the recept or and G(i alpha 2) associates with the receptor, whereas G(i alpha 3) and the G(beta) subunits remain coupled to the delta receptor. These findings reveal dynamic changes in the G proteins associated with the receptor after agonist binding that may be linked to the activation of the delta receptor. In addition to pertussis toxin-sensitive G protei ns, the delta receptor physically interacts with the pertussis torn-in sensitive G proteins G(q alpha) and G(z alpha). These interactions may be critical in linking delta receptors to phospholipase C. The divers ity of G proteins associated with the delta opioid receptor may form t he basis for the selective coupling of these receptors to multiple cel lular effector systems.