Opioid Receptor Family

Opioid receptors (OPRs) are a group of inhibitory G protein-coupled receptors with opioids as ligands. The opioid receptors are widely distributed in the brain, spinal cord and digestive tract, especially in the limbic system, as well as in nociceptive pathways and along the hypothalamic-pituitary-adrenal axis. In these neural circuits, the opioid system regulates addictive and emotional behaviors and controls responses to pain or stress. There are four major subtypes of opioid receptors have been cloned in many species, namely δ-opioid receptor, OPRD; κ-opioid receptor, OPRK; nociceptin receptor, OPRL; μ-opioid receptor, OPRM.

The δ receptors are discretely distributed in the CNS, with highest levels in the olfactory bulb, neocortex, caudate putamen, nucleus accumbens, and amygdala, which are associated with analgesia, gastrointestinal motility, mood behavior as well as cardiovascular regulation. In the spinal cord, δ receptors are present in dorsal horn where they play a role in mediating the analgesic effects of δ agonists. The κ receptors are predominantly distributed in the cerebral cortex, nucleus accumbens, claustrum and hypothalamus of rat and mouse, and have been implicated in the regulation of nociception, diuresis, feeding, neuroendocrine and immune system functions. The μ receptors are distributed throughout the neuraxis, among which the thalamus, caudate putamen, neocortex, nucleus accumbens, amygdala, interpeduncular complex, and inferior and superior colliculi are most abundant with high concentrations. Various functions of μ receptors are identified, e.g., pain and analgesia, respiratory and cardiovascular functions, thermoregulation, intestinal transit, feeding, mood, hormone secretion, and immune functions. Nociceptin receptors are present at relatively high density in selected regions of rat cortex, anterior olfactory nucleus, lateral septum, ventral forebrain, hippocampus, hypothalamus, amygdala, substantia nigra, ventral tegmental area, locus coeruleus, brain stem nuclei and in the dorsal horn of spinal cord, suggesting a role in motor and aggressive behaviors, reinforcement and reward, nociception, the stress response, and control of autonomic and immune functions.

Here show the four major subtypes of opioid receptors, namely OPRD1, OPRK1, OPRL1, OPRM1. OPRD1 recognizes enkephalins as its preferred endogenous ligands. Dynorphins A and B and α-neoendorphin appear to be the endogenous ligands for OPRK1. OPRM1 binds morphine with high affinity and sensitivity. The only known ligand for OPRL1 is nociceptin itself.

Human Opioid Receptors Members
OPRD1	OPRL1

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