Mu opioid receptor

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Active and inactive mu-opioid receptors.^[1]
opioid receptor, mu 1
Identifiers
Symbol	OPRM1
HUGO	8156
Entrez	4988
OMIM	600018
RefSeq	NM_000914
UniProt	P35372
Other data
Locus	Chr. 6 q24-q25

The μ opioid receptors (MOR) can exist either presynaptically or postsynaptically depending upon cell types. MOR can mediate acute changes in neuronal excitability via "disinhibition" of presynaptic release of GABA (see works from Charles Chavkin and Roger Nicoll). In contrast, chronic activation of MOR causes the collapse of dendritic spines via post-synaptic mechanisms (see works from Dezhi Liao and Horace Loh). The physiological and pathological roles of these two distinct mechanisms remain to be clarified. Perhaps, both might be involved in opioid addiction and opioid-induced deficits in cognition.

The μ-receptors exist mostly presynaptically in the periaqueductal gray region, and in the superficial dorsal horn of the spinal cord (specifically the substantia gelatinosa of Rolando). Other areas where μ-receptors have been located include the external plexiform layer of the olfactory bulb, the nucleus accumbens, in several layers of the cerebral cortex and in some of the nuclei of the amygdala. The μ-receptor has high affinity for enkephalins and beta-endorphin but low affinity for dynorphins. The opioid alkaloids morphine and codeine are known to bind to this receptor.

Activation of the μ receptor by an agonist such as morphine causes analgesia, sedation, reduced blood pressure, itching, nausea, euphoria, decreased respiration, miosis (constricted pupils) and decreased bowel motility often leading to constipation. Some of these effects, such as sedation, euphoria and decreased respiration, tend to disappear with continued use as tolerance develops. Analgesia, miosis and reduced bowel motility tend to persist; little tolerance develops to these effects. Tolerance develops to different effects at different rates largely because these effects are caused by activation of different μ-receptor subtypes . Stimulation of μ₁-receptors blocks pain while stimulation of μ₂-receptor causes respiratory depression and constipation [1].

Tolerance to respiratory depression develops quickly. In the drug naïve individual respiratory depression is the primary way overdoses kill. Less commonly massive overdoses have been known to cause circulatory collapse. Opioid overdoses can be rapidly reversed with any of several opioid antagonists: naloxone, or naltrexone, differing primarily in their duration of action and potency. While commonly referred to as antagonists, and when used to treat an overdose they do appear to function as such, naloxone & naltrexone are inverse agonists.

[edit] References

^ Zhorov BS, Ananthanarayanan VS. Homology models of mu-opioid receptor with organic and inorganic cations at conserved aspartates in the second and third transmembrane domains. Arch Biochem Biophys. 37:31-49, 2000.