Kappa-type opioid receptor (OPRK1) (OPRK1)

The Kappa-type opioid receptor (OPRK1) is a G protein-coupled receptor (GPCR) that primarily mediates the effects of the endogenous opioid peptide dynorphin (UniProt: P41145). It is widely expressed in the central nervous system, particularly in the cerebral cortex, hippocampus, and spinal cord, where it regulates nociception, mood, and stress responses (NCBI Gene: 4986). Unlike the mu-opioid receptor, activation of OPRK1 is associated with dysphoria, sedation, and psychotomimetic effects, which makes it a significant target for treating psychiatric disorders and addiction (PubMed: PMC2852135). Naltrexone is a long-acting opioid antagonist that binds to OPRK1 with high affinity, blocking its signaling and reducing the rewarding effects of alcohol and opioids (StatPearls: NBK534811). This interaction is crucial for its clinical use in managing substance use disorders by preventing relapse and reducing cravings. Additionally, OPRK1 is a target for novel analgesics and antipruritic agents, such as difelikefalin, which aim to provide relief without the side effects associated with mu-opioid agonists (PubChem: CID 5360515).

Other names

Kappa opioid receptorKORKOR-1OPRK

Competitive antagonism of the kappa-type opioid receptor; inhibition of adenylate cyclase and modulation of G protein-coupled inward-rectifier potassium channels via Gi/Go signaling pathways (UniProt: P41145).