Ligand-dependent spatiotemporal signaling profiles of the μ-opioid receptor are controlled by distinct protein-interaction networks.

ABSTRACT: Ligand-dependent differences in the regulation and internalization of the μ-opioid receptor (MOR) have been linked to the severity of adverse effects that limit opiate use in pain management. MOR activation by morphine or [d-Ala²,N-MePhe⁴, Gly-ol]enkephalin (DAMGO) causes differences in spatiotemporal signaling dependent on MOR distribution at the plasma membrane. Morphine stimulation of MOR activates a Gα_i/o-Gβγ-protein kinase C (PKC) α phosphorylation pathway that limits MOR distribution and is associated with a sustained increase in cytosolic extracellular signal-regulated kinase (ERK) activity. In contrast, DAMGO causes a redistribution of the MOR at the plasma membrane (before receptor internalization) that facilitates transient activation of cy

SUBMITTER: Civciristov S 

PROVIDER: S-EPMC6827304 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature