Mechanistic insights into the therapeutic properties of delta opioid receptor - PubMed
3 hours ago
- #receptor dynamics
- #delta opioid receptor
- #ligand efficacy
- The delta opioid receptor (DOR) is a target for pain, anxiety, and depression, but no DOR-based drugs are clinically available.
- Different ligands modulate DOR function: full agonists cause rapid internalization, partial agonists slow internalization, and antagonists increase cell-surface DOR levels.
- High-resolution structures of ligand-bound DOR-Gi1 complexes explain ligand selectivity, potency, and efficacy.
- Single-molecule FRET reveals DOR samples active, preactive, and inactive states, with transitions tuned by ligand efficacy and G protein coupling.
- The endogenous agonist met-enkephalin stabilizes the active state and catalyzes transitions between active and inactive states.
- Findings provide insights into ligand-receptor interactions and dynamics, aiding development of DOR-targeted therapeutics.