Vol. 281, Issue 3, 1476-1486, 1997

Changes in the Association of G Protein Subunits with the Cloned Mouse Delta Opioid Receptor on Agonist Stimulation

Susan F. Law and Terry Reisine

Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania

G proteins couple delta opioid receptors to multiple cellular effector systems and are critical components of the delta opioid signal transduction cascade. To investigate the physical association of delta opioid receptors with G proteins, the cloned mouse delta opioid receptor was solubilized, and the G proteins associated with the receptor were identified through coimmunoprecipitation of the receptor/G protein complexes with antisera directed against different G and G subunits. The delta receptor associates with G_i1, G_i3, G_o, G₁ and G₂ subtypes. On agonist binding to the receptor, a greater proportion of the receptor is associated with G_i than with G_o, G_i1 dissociates from the receptor and G_i2 associates with the receptor, whereas G_i3 and the G 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 proteins, the delta receptor physically interacts with the pertussis toxn-insensitive G proteins G_q and G_z. These interactions may be critical in linking delta receptors to phospholipase C. The diversity of G proteins associated with the delta opioid receptor may form the basis for the selective coupling of these receptors to multiple cellular effector systems.