Kappa-opioid receptor (KOR)

The Kappa-opioid receptor (KOR) is a G protein-coupled receptor encoded by the OPRK1 gene in humans[3]. It is one of four related receptors in the opioid receptor family, sharing approximately 70% sequence identity in their transmembrane domains with the mu-opioid receptor (MOR) and delta-opioid receptor (DOR)[6][10]. KOR primarily binds the endogenous opioid peptide dynorphin and mediates effects on nociception, consciousness, motor control, and mood regulation[3]. KOR has emerged as an important therapeutic target because, unlike traditional mu-opioid receptor agonists, compounds that selectively target KOR can provide pain relief without the high addiction potential associated with drugs like morphine and fentanyl[7][8]. Recent research has focused on developing pathway-selective KOR ligands that preferentially signal through G protein rather than arrestin pathways to minimize side effects[7]. Beyond pain management, KOR has shown promise as a target for treating pruritus (itching), epilepsy, and potentially as an adjunct in cancer therapy, particularly for gliomas[2][8]. The receptor's structure has been extensively studied using techniques like X-ray crystallography and molecular dynamics simulations to better understand its activation mechanisms and develop more effective, safer drugs[7][10].

Other names

κ-opioid receptorKappa receptorKOR-1OP2KOPrOPRK1

KOR exerts its effects through: - G protein signaling pathways (primarily Gi protein) - Inhibition of adenylyl cyclase - Biased signaling (G protein vs. arrestin pathways) - Regulation of p38 MAPK pathway (relevant for anti-tumor effects)