Kappa-type and Delta-type opioid receptors (KOR, DOR)

Kappa-type and delta-type opioid receptors are G protein-coupled receptors (GPCRs) belonging to the opioid receptor family, alongside the mu-opioid receptor[5][9]. The kappa opioid receptor (KOR; OPRK1) is primarily activated by endogenous dynorphins, whereas the delta opioid receptor (DOR; OPRD1) responds preferentially to enkephalins[5][7][9]. Both receptors are widely expressed in the central and peripheral nervous systems, where they modulate pain transmission, mood, stress response, and other physiological functions[1][5][7][9]. KOR and DOR agonists produce analgesia but display distinct side effect profiles: kappa agonists are less likely to induce euphoria or addiction but may cause dysphoria or hallucinations, while delta agonists are under investigation for modulation of emotional states and pain with fewer adverse gastrointestinal and respiratory effects compared to mu-opioid receptor agonists[1][5][9]. Both receptors are targets for novel analgesics with the aim of reducing opioid-related adverse effects and abuse potential, though development is complicated by their pharmacodynamics and central actions[1][4][6][7].

Other names

Kappa opioid receptorDelta opioid receptorKORDOROP2 (for kappa)OP1 (for delta)OPRK1 (gene symbol for kappa-type)OPRD1 (gene symbol for delta-type)

Agonist binding to KOR/DOR activates inhibitory Gi/o proteins, reducing intracellular cAMP and hyperpolarizing neurons to inhibit neurotransmitter release; Antagonists block receptor-mediated signaling, preventing endogenous or exogenous opioid effects; Biased agonists can preferentially activate G-protein or beta-arrestin pathways, affecting efficacy and side effect profiles