The Only Way Is Up: Preventing Opioid Tolerance by Promoting Cell Surface Expression of MOR-DOR Heterodimers?

Abstract

The development of morphine tolerance is a complicated process likely involving many different factors. Both μ (MOR) and δ (DOR) opi-oid receptors are known to influence morphine tolerance. Significantly, the role of both receptors appears to change during the acquisition of tolerance, and for both these receptors, regulated receptor trafficking may influence these changes. Morphine does not induce substantial endocytosis and recycling of MORs but appears to increase surface expression of DOR, which, under many conditions, is not efficiently transported to the cell surface. A recent report demonstrates that members of the family of Receptor Transporter Proteins increase surface expression of MOR-DOR heterodimers. The implications of these findings with regard to morphine tolerance are discussed.