Central nervous system opioid receptors

Central nervous system opioid receptors encompass a family of G protein-coupled receptors (GPCRs), primarily the mu (μ, MOP), delta (δ, DOP), and kappa (κ, KOP) subtypes, along with the related nociceptin receptor (NOP), widely distributed in brain regions like the cortex, limbic system, thalamus, periaqueductal gray, and spinal dorsal horn. These receptors mediate endogenous opioid signaling via peptides such as enkephalins, endorphins, and dynorphins, coupling to Gi/Go proteins to inhibit adenylyl cyclase, hyperpolarize neurons via K+ channels, and suppress neurotransmitter release by blocking Ca2+ channels, thereby reducing neuronal excitability. They play critical roles in analgesia, reward, mood regulation, and seizure modulation, with mu receptors driving most therapeutic pain relief but also euphoria and dependence. Dysregulation contributes to chronic pain, epilepsy (e.g., upregulated binding in temporal lobe epilepsy), addiction, and trauma responses. Exogenous opioids like morphine and fentanyl primarily target mu receptors for analgesia but pose high risks of respiratory depression, tolerance, and abuse liability, prompting research into biased agonists and subtype-selective drugs to improve safety. Imaging studies reveal binding variations by age, gender, and disease, aiding patient stratification.

Other names

opioid receptors (OR)mu opioid receptor (MOP-R, μ-OR)delta opioid receptor (DOP-R, δ-OR)kappa opioid receptor (KOP-R, κ-OR)nociceptin/orphanin FQ receptor (NOP-R, ORL-1)

G-protein activation (Gi/Go family) leading to GDP-GTP exchange, inhibition of adenylyl cyclase, activation of inwardly rectifying K+ channels, inhibition of voltage-gated Ca2+ channels, beta-arrestin recruitment for desensitization/internalization