OPRD1

OPRD1 Full Name

opioid receptor, delta 1

OPRD1 Introduction

The Delta Opioid Receptor 1 (δ1-OR) is one of the four major subtypes of opioid receptors in the G-protein-coupled receptor (GPCR) superfamily, alongside mu (μ), kappa (κ), and the nociceptin/orphanin FQ peptide (NOP) receptor. It is encoded by the OPRD1 gene. This receptor is a primary target for endogenous opioid peptides, notably the enkephalins. While its analgesic properties are well-recognized, the δ1-OR is distinguished by its prominent roles in modulating emotional responses, mood, and motivational behaviors, often producing effects that contrast with those of the mu opioid receptor. The regions of the brain where the δ-opioid receptor is largely expressed vary from species model to species model. In humans, the δ-opioid receptor is most heavily expressed in the basal ganglia and neocortical regions of the brain.

Figure. Structure of Delta Opioid Receptor 1.

Signal Mechanism
OPRD1 mainly binds to the Gi/o family of G proteins. After activation by agonists such as enkephalin, the receptor undergoes conformational changes, resulting in:
Inhibition of adenylate cyclase: The dissociated G α i subunit inhibits adenylate cyclase, reducing the level of the key second messenger cyclic AMP (cAMP) in cells. This reduces the activity of protein kinase A (PKA) and affects downstream gene transcription.
Regulation of ion channels: The released G β - γ subunits directly activate inward rectifying potassium channels (GIRKs), leading to membrane hyperpolarization and reduced neuronal excitability. At the same time, they inhibit voltage-gated calcium channels (VGCC) and reduce neurotransmitter release from presynaptic terminals.

Function
The endogenous system of opioid receptors is known for its analgesic potential; However, the exact role of delta opioid receptor activation in pain regulation remains largely controversial. This also depends on the model at hand, as it is known that receptor activity varies by species. The activation of δ receptors produces analgesic effects and may be an important enhancer of μ - opioid receptor agonists. However, it seems that delta excitability provides a powerful enhancing effect for any mu excitability. Therefore, even selective mu agonists can cause analgesia under appropriate conditions, while not causing any analgesia under other conditions. However, some people believe that the pain regulated by μ - opioid receptors and δ - opioid receptors are different types, and assert that DOR regulates the perception of chronic pain, while MOR regulates acute pain. δ 1-OR regulates the reward circuit of the brain. Its activities usually offset the rewarding effects of drug abuse and natural rewards. The antagonistic effect of δ 1-OR can enhance the reward properties of substances such as cocaine and morphine, while agonists may weaken them, indicating its complex bidirectional role in addiction.

Alternate Names for OPRD1

OPRD1; opioid receptor, delta 1; OPRD; delta-type opioid receptor; DOR-1; D-OR-1; delta opioid receptor 1;