Opioid receptor

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Vidit Bhargava, M.B.B.S [2]

Overview

Opioid receptors are a group of G-protein coupled receptors with opioids as ligands. The endogenous opioids are dynorphins, enkephalins, endorphins, endomorphins and nociceptin/orphanin FQ. The opioid receptors are ~40% identical to somatostatin receptors (SSTRs).

Types of receptors

There are three major subtypes of opioid receptors: [1]

Greek letter name Name based on order of discovery Subtypes
delta Opioid receptor (δ) OP1 δ1, δ2
kappa Opioid receptor (κ) OP2 κ1, κ2, κ3
mu Opioid receptor (μ) OP3 μ1, μ2, μ3
Nociceptin Opioid receptor OP4 ORL1

Sigma receptors (σ) were once considered to be opioid receptors, but are not usually currently classified as such.

The receptors were named using the first letter of the first ligand that was found to bind to them. Morphine was the first chemical shown to bind to mu receptors. The first letter of the drug morphine is `m', but in biochemistry there is a tendency to use Greek letters, thus turning the 'm' to μ. Similarly a drug known as ketocyclazocine was first shown to attach itself to kappa receptors.[2]

The opioid receptor types are ~70% identical with differences located at N and C termini. The μ receptor (the μ represents morphine) is perhaps the most important. It is thought that the G protein binds to the third intracellular loop of the opioid receptors. Both in mice and humans the genes for the various receptor subtypes are located on different chromosomes.

Separate subtypes have been identified in human tissue. Research has so far failed to identify the genetic evidence of the subtypes, and it is thought that they arise from post-translational modification of cloned receptor types.[3]

An additional opioid receptor has been identified and cloned based on homology with the cDNA. This receptor is known as the nociceptin receptor or ORL 1 receptor.

An IUPHAR subcommittee has suggested that appropriate terminology for the 3 typical (μ, δ, κ) and the atypical (nociceptin) receptors, should be MOR, DOR, KOR and NOR respectively.

Major subtypes

There are four major subtypes of opioid receptors:[4]

Receptor Subtypes Location[5][6] Function[5][6]
delta (δ)
DOR
OP1 (I)
δ1, δ2
kappa (κ)
KOR
OP2 (I)
κ1, κ2, κ3
mu (μ)
MOR
OP3 (I)
μ1, μ2, μ3 μ1:

μ2:

μ3:

  • Possible vasodilation
Nociceptin receptor
NOP
OP4
ORL1
  • Anxiety
  • Depression
  • Appetite
  • Development of tolerance to μ agonists

(I). Name based on order of discovery

References

  1. Corbett AD, Henderson G, McKnight AT, Paterson SJ (2006).75 years of opioid research: the exciting but vain quest for the Holy Grail. Brit. J. Pharmacol.147, S153–S162
  2. http://opioids.com/narcotic-drugs/chapter-3.html
  3. Fries, DS (2002). Opioid Analgesics. In Williams DA, Lemke TL. Foye's Principles of Medicinal Chemistry (5 ed.). Philadelphia: Lippincott Williams & Wilkins. ISBN 0-683-30737-1.
  4. Corbett AD, Henderson G, McKnight AT, Paterson SJ (2006). "75 years of opioid research: the exciting but vain quest for the Holy Grail". Br. J. Pharmacol. 147 Suppl 1 (Suppl 1): S153–62. doi:10.1038/sj.bjp.0706435. PMC 1760732. PMID 16402099.
  5. 5.0 5.1 Stein C, Schäfer M, Machelska H (August 2003). "Attacking pain at its source: new perspectives on opioids". Nat. Med. 9 (8): 1003–8. doi:10.1038/nm908. PMID 12894165.
  6. 6.0 6.1 Fine PG, Portenoy RK (2004). "Chapter 2: The Endogenous Opioid System" (PDF). A Clinical Guide to Opioid Analgesia. McGraw Hill.

See also

External links

de:Opioidrezeptor fi:Opioidireseptori


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