Nociceptin receptor
Encyclopedia
The nociceptin receptor or NOP also known as the orphanin FQ receptor or kappa-type 3 opioid receptor is a protein
that in humans is encoded by the OPRL1 (opioid receptor-like 1) gene
. The nociceptin receptor is a G protein-coupled receptor
whose natural ligand
is known as nociceptin
or orphanin FQ, a 17 amino acid neuropeptide
. This receptor is involved in the regulation of numerous brain activities, particularly instinctive and emotional behaviors.
or by inhibiting GABA
to affect dopamine levels. Within the central nervous system
its action can be either similar or opposite to those of opioids depending on their location. It controls a wide range of biological functions ranging from nociception
to food intake, from memory
processes to cardiovascular and renal functions, from spontaneous locomotor activity
to gastrointestinal motility, from anxiety
to the control of neurotransmitter
release at peripheral and central sites.
and buprenorphine
have been demonstrated to bind to nociceptin receptors, but this binding is relatively insignificant compared to their activity at other opioid receptors. More recently a range of selective ligands for ORL-1 have been developed, which show little or no affinity to other opioid receptors and so allow ORL-1 mediated responses to be studied in isolation.
while nociceptin antagonists such as JTC-801
may have analgesic
and antidepressant
qualities.
The novel drug buprenorphine
is a partial agonist
at ORL 1 receptors while its metabolite norbuprenorphine
is a full agonist at these receptors.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that in humans is encoded by the OPRL1 (opioid receptor-like 1) gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
. The nociceptin receptor is a G protein-coupled receptor
G protein-coupled receptor
G protein-coupled receptors , also known as seven-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptor, and G protein-linked receptors , comprise a large protein family of transmembrane receptors that sense molecules outside the cell and activate inside signal...
whose natural ligand
Ligand (biochemistry)
In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. In a narrower sense, it is a signal triggering molecule, binding to a site on a target protein.The binding occurs by intermolecular forces, such as ionic bonds, hydrogen...
is known as nociceptin
Nociceptin
Nociceptin or orphanin FQ, a 17 amino acid neuropeptide, is the endogenous ligand for the nociceptin receptor . It is derived from the prepronociceptin protein, as are a further 2 peptides, nocistatin & NocII...
or orphanin FQ, a 17 amino acid neuropeptide
Neuropeptide
Neuropeptides are small protein-like molecules used by neurons to communicate with each other. They are neuronal signaling molecules, influence the activity of the brain in specific ways and are thus involved in particular brain functions, like analgesia, reward, food intake, learning and...
. This receptor is involved in the regulation of numerous brain activities, particularly instinctive and emotional behaviors.
Mechanism
Nociceptin is thought to be an endogenous antagonist of dopamine transport that may act either directly on dopamineDopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
or by inhibiting GABA
GABA antagonist
GABA antagonists are drugs which inhibit the action of GABA. In general these drugs produce stimulant and convulsant effects, and are mainly used for counteracting overdose of sedative drugs....
to affect dopamine levels. Within the central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
its action can be either similar or opposite to those of opioids depending on their location. It controls a wide range of biological functions ranging from nociception
Nociception
Nociception is defined as "the neural processes of encoding and processing noxious stimuli." It is the afferent activity produced in the peripheral and central nervous system by stimuli that have the potential to damage tissue...
to food intake, from memory
Memory
In psychology, memory is an organism's ability to store, retain, and recall information and experiences. Traditional studies of memory began in the fields of philosophy, including techniques of artificially enhancing memory....
processes to cardiovascular and renal functions, from spontaneous locomotor activity
Locomotor activity
Locomotor activity refers to the movement from place to place. In psychopharmacology, locomotor activity of lab animals is often monitored to assess the behavioural effects of these drugs. Locomotor activity is useful and less robust than most behavioural tests such as operant conditioning and...
to gastrointestinal motility, from anxiety
Anxiety
Anxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...
to the control of neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
release at peripheral and central sites.
Selective ligands
Several commonly used opioid drugs including etorphineEtorphine
Etorphine is a semi-synthetic opioid possessing an analgesic potency approximately 200 times that of morphine. It was first prepared in 1960 from oripavine, which does not generally occur in opium poppy extract but rather in "poppy straw" and in related plants, Papaver orientale and Papaver...
and buprenorphine
Buprenorphine
Buprenorphine is a semi-synthetic opioid that is used...
have been demonstrated to bind to nociceptin receptors, but this binding is relatively insignificant compared to their activity at other opioid receptors. More recently a range of selective ligands for ORL-1 have been developed, which show little or no affinity to other opioid receptors and so allow ORL-1 mediated responses to be studied in isolation.
Agonists
- BuprenorphineBuprenorphineBuprenorphine is a semi-synthetic opioid that is used...
(not selective for ORL-1, also partial agonist of µ-opioid and δ-opioid receptors, and competitive antagonist of ϰ-opioid receptors) - NociceptinNociceptinNociceptin or orphanin FQ, a 17 amino acid neuropeptide, is the endogenous ligand for the nociceptin receptor . It is derived from the prepronociceptin protein, as are a further 2 peptides, nocistatin & NocII...
- NorbuprenorphineNorbuprenorphineNorbuprenorphine is the primary active metabolite of buprenorphine. Norbuprenorphine acts as a μ-opioid, δ-opioid, and nociceptin receptor full agonist, as well as a κ-opioid receptor partial agonist. Norbuprenorphine crosses the blood-brain-barrier similarly to buprenorphine and likely contributes...
(not selective for ORL-1, also full agonist at μ-opioid and δ-opioid receptors) - NNC 63-0532NNC 63-0532NNC 63-0532 is an nociceptoid drug used in scientific research. It acts as a potent and selective agonist for the nociceptin receptor, also known as the ORL-1 receptor...
- Ro64-6198Ro64-6198Ro64-6198 is an nociceptoid drug used in scientific research. It acts as a potent and selective agonist for the nociceptin receptor, also known as the ORL-1 receptor, with over 100x selectivity over other opioid receptors...
- Ro65-6570
- SCH-221,510
- SR-16435 (mixed mu / nociceptin partial agonist)
Applications
ORL 1 agonists are being studied as treatments for heart failure and migraineMigraine
Migraine is a chronic neurological disorder characterized by moderate to severe headaches, and nausea...
while nociceptin antagonists such as JTC-801
JTC-801
JTC-801 is an opioid analgesic drug used in scientific research.JTC-801 is a selective antagonist for the nociceptin receptor, also known as the ORL-1 receptor. This was the fourth opioid receptor to be discovered, and is still the least understood...
may have analgesic
Analgesic
An analgesic is any member of the group of drugs used to relieve pain . The word analgesic derives from Greek an- and algos ....
and antidepressant
Antidepressant
An antidepressant is a psychiatric medication used to alleviate mood disorders, such as major depression and dysthymia and anxiety disorders such as social anxiety disorder. According to Gelder, Mayou &*Geddes people with a depressive illness will experience a therapeutic effect to their mood;...
qualities.
The novel drug buprenorphine
Buprenorphine
Buprenorphine is a semi-synthetic opioid that is used...
is a partial agonist
Partial agonist
Partial agonists bind and activate a given receptor, but have only partial efficacy at the receptor relative to a full agonist...
at ORL 1 receptors while its metabolite norbuprenorphine
Norbuprenorphine
Norbuprenorphine is the primary active metabolite of buprenorphine. Norbuprenorphine acts as a μ-opioid, δ-opioid, and nociceptin receptor full agonist, as well as a κ-opioid receptor partial agonist. Norbuprenorphine crosses the blood-brain-barrier similarly to buprenorphine and likely contributes...
is a full agonist at these receptors.