κ Opioid Receptors

The κ (kappa) opioid receptor is a member of the opioid family of G-protein-coupled receptors that in humans is encoded by the OPRK1 gene. Three variants (κ1, κ2, and κ3) have been characterized although only one cDNA clone has been identified.  Among the opioid peptides, dynorphins primarily activate κ opioid receptors and have very low affinity for μ or δ receptors, and are considered to be the primary endogenous ligands.  Kappa opioid receptors are the most abundant opioid receptors in the brain, and are located predominantly in the cerebral cortex, nucleus accumbens, claustrum and hypothalamus and are also found in the spinal cord, and peripheral tissues.  The κ receptor system is involved in the regulation of nociception, diuresis, feeding and neuroendocrine secretions and is a central player in the reward and mood processes.  Dysregulation of the κ receptor system has been implicated in stress and consequences such as depression, anxiety, anhedonia, and in alcohol and drug addiction.  Kappa receptor agonists are analgesic and have been used clinically in the treatment of pain.

Further reading

James et al (1982) Selectivity of dynorphin for kappa opioid receptors. Life Sci. 31(12-13):1331 PMID: 6128656

Lalanne et al (2014) The kappa opioid receptor: from addiction to depression, and back. Front Psychiatry 5 170 PMID: 25538632

Matuskey et al (2019) Social status and demographic effects of the kappa opioid receptor: a PET imaging study with a novel agonist radiotracer in healthy volunteers. Neuropsychopharmacology 44(10) 1714 PMID: 30928993