Regulation Of Cell Surface Expression Of Delta Opioid Receptor In Dorsal Root Ganglion Neurons

The opioid system serves inhibitory functions in pain transmission. Delta-andmu-opioid receptors are expressed in small dorsal root ganglion (DRG) neuronsand mediate the effects of endogenous opioid peptides and analgesics.Interestingly, while mu-opioid receptors are transported along the constitutivepathway, δ-opioid receptors (DORs) are sorted into the regulated pathway and areoften found to be associated with large dense-core vesicles (LDCVs). In the firstpart, we found that membrane insertion of DORs can be triggered by nociceptivestimulus-induced Ca2+ elevation that causes exocytosis of LDCVs. Deletion of thepreprotachykinin A gene eliminates the sorting of DORs into the regulatedsecretory pathway. We also found that deletion of the preprotachykinin A geneeliminates membrane insertion of DORs induced by stimulus and attenuates theagonist-induced long-lasting exocytosis of LDCVs. In the second part, wedemonstrated the regulation of surface expression of DORs in DRG neuronsindependent of Ca2+ elevation. We found that naltrindole, a pharmacologicalchaperone of DOR, enhance both the constitutive and regulated pathway of DORexpression by facilitated the maturation and inhibiting the degradation of DORprecursor in endoplasmic retinum. Taken together, these studies demonstrated thatsurface expression of DORs in small DRG neurons can be regulated by multiplefactors. And the regulation may have significant implications for modulation ofopioid's analgesic effect and development of new analgesic drugs.