TABLE 1

Cellular adaptations after MOP-r activation by internalizing agonists

Adaptive Process Time Scale (after DAMGO treatment of HEK 293 cells expressing MOP-r) Apparent Functional Consequences
MOP-r - effector functional un-coupling after receptor phosphorylation by GRKs, PKA, or PKC. Within minutes.a Rapid loss of agonist signaling (e.g., reduced inhibition of adenylyl cyclase) after receptor phosphorylation.
Endocytosis of MOP-r via clathrin-coated pits. Within a few minutes. Removal of desensitized receptor from plasma membrane.
Endosomal sorting and recycling of reactivated MOP-r to plasma membrane. Within 1 h. Recycled receptors restore agonist signaling.
Increased levels of cAMP (with increased PKA activity); other postreceptor adaptations. Longer than 1 h, but less than 8 h. Functional antagonism of MOP-r signaling; physical dependence.

  • GRK, G protein-coupled receptor kinase; PKA, protein kinase A; PKC, protein kinase C.

  • ↵ a From Alvarez et al. (2002). The biochemical techniques used by Koch et al. (2005) are not suited to an estimation of the initial rate of MOP-r desensitization