Morphine Induces Endocytosis of Neuronal μ-opioid Receptors Through the Sustained Transfer of Gα Subunits to RGSZ2 Proteins

Abstract

In the nervous system, morphine induces a strong desensitization before promoting the phosphorylation and recycling of MORs. The long-term sequestering of morphine-activated Galpha subunits by certain RGS proteins reduces the responses to this opioid in neurons. This phenomenon probably increases free Gbetagamma dimers in the receptor environment and leads to GRK phosphorylation and internalization of the MORs. Although, the internalization of the MORs permits the transfer of opioid-activated Galpha subunits to the RGSZ2 proteins, it interferes with the stabilization of this regulatory process and recycled MORs recover the control on these Galpha subunits and opioid tolerance develops slowly.