Receptorsmu

Receptorsmu, commonly referred to as the mu opioid receptor (MOR), is a G protein-coupled receptor in the opioid receptor family. It binds endogenous opioid peptides as well as a range of exogenous opioid drugs, mediating analgesia and other physiological effects.

Structurally, MOR is a seven-transmembrane domain receptor. It primarily couples to Gi/o proteins, leading to inhibition of adenylyl cyclase and a decrease in cAMP, and to the opening of potassium channels while inhibiting voltage-gated calcium channels. This signaling reduces neurotransmitter release at synapses. Beta-arrestin–dependent pathways contribute to receptor desensitization and internalization, influencing tolerance and other long-term responses.

Distribution and roles are diverse. MOR is abundant in the central nervous system, including the periaqueductal gray, nucleus accumbens, ventral tegmental area, and dorsal horn of the spinal cord, as well as in peripheral tissues such as the gastrointestinal tract. Physiologically, MOR activation produces analgesia, euphoria, respiratory depression, miosis, and decreased gastrointestinal motility, and it modulates reward and mood.

Ligands and pharmacology. Endogenous ligands include beta-endorphin and enkephalins. Exogenous agonists include morphine, heroin, fentanyl, and methadone; antagonists such as naloxone and naltrexone block MOR signaling. Clinically, MOR mediates the effectiveness and side effects of opioid analgesics, with tolerance, dependence, and withdrawal as common consequences of sustained use. Genetic variation in the MOR gene (OPRM1) influences receptor function and individual responses to opioids; the A118G (rs1799971) polymorphism is among the best studied in this regard.

Research continues to clarify MOR’s roles, signaling biases, and potential as a therapeutic target to improve analgesia while reducing adverse effects.