Expression of the third intracellular loop of the δ-opioid receptor alters G protein signaling

Previous published results from our laboratory concerning the interactions of opioid receptors with G proteins have shown that the third intracellular loop of the delta-opioid receptor is responsible for coupling to G proteins and inhibition of adenylyl cyclase. Based on these observations and in order to design and develop analogues that could potentially block or activate selectively in vivo the interactions of these receptors with G proteins or other downstream signaling components, we constructed a minigene encoding the third intracellular loop of delta-opioid receptor (pDORi3). Our results indicate that the pDORi3 minigene is able to interact specifically with the G proteins, in mu-HEK293 cells. These observations underlie the significance of the third intracellular loop for signal transfer of mu-opioid receptor, and suggest a strategy whereas the receptor-G protein interface may represent a target for novel receptor drug development.