Opioid receptor

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:

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.

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.

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:

Receptor	Subtypes	Location	Function
delta (δ) DOR OP1 (I)	δ1, δ2	Brain Pontine nuclei Amygdala Olfactory bulbs deep Cortex Peripheral sensory neurons	Analgesia Antidepressant effects Convulsant effects Physical dependence Perhaps of mu-opioid receptor-mediated respiratory depression
kappa (κ) KOR OP2 (I)	κ1, κ2, κ3	Brain Hypothalamus Periaqueductal gray Claustrum Spinal cord substantia gelatinosa Peripheral sensory neurons	Analgesia Anticonvulsant effects Dissociative & Deliriant effects Diuresis Dysphoria Miosis Neuroprotection Sedation
mu (μ) MOR OP3 (I)	μ1, μ2, μ3	Brain Cortex (laminae III and IV) Thalamus striosomes Periaqueductal gray Rostral ventromedial medulla Spinal cord substantia gelatinosa Peripheral sensory neurons Intestinal tract	μ1: Analgesia Physical dependence μ2: Respiratory depression Miosis Euphoria Reduced GI motility Physical dependence μ3: Possible vasodilation
Nociceptin receptor NOP OP4	ORL1	Brain cortex Amygdala Hippocampus Septal nuclei Habenula Hypothalamus Spinal cord	Anxiety Depression Appetite Development of tolerance to μ agonists

(I). Name based on order of discovery

See also

• Opioid antagonist
• http://opioids.com/receptors/index.html

External links

• IUPHAR GPCR Database - Opioid Receptors
• Opioid+Receptors at the US National Library of Medicine Medical Subject Headings (MeSH)
• Calculated spatial position of mu-opioid receptor in the lipid bilayer, inactive state with antagonist and active state with agonist