Opioid receptors are a group of inhibitory G protein-coupled receptors with opioids as ligands. The endogenous opioids are dynorphins,enkephalins,endorphins,endomorphins and nociceptin. The opioid receptors are ~40% identical to somatostatin receptors (SSTRs). Opioid receptors are distributed widely in the brain,in the spinal cord,on peripheral neurons,and digestive tract.
An enkephalin is a pentapeptide involved in regulating nociception in the body. The enkephalins are termed endogenous ligands,as they are internally derived and bind to the body's opioid receptors. Discovered in 1975,two forms of enkephalin have been found,one containing leucine ("leu"),and the other containing methionine ("met"). Both are products of the proenkephalin gene.
β-Endorphin (beta-endorphin) is an endogenous opioid neuropeptide and peptide hormone that is produced in certain neurons within the central nervous system and peripheral nervous system. It is one of three endorphins that are produced in humans,the others of which include α-endorphin and γ-endorphin.
Opioid peptides or opiate peptides are peptides that bind to opioid receptors in the brain;opiates and opioids mimic the effect of these peptides. Such peptides may be produced by the body itself,for example endorphins. The effects of these peptides vary,but they all resemble those of opiates. Brain opioid peptide systems are known to play an important role in motivation,emotion,attachment behaviour,the response to stress and pain,control of food intake,and the rewarding effects of alcohol and nicotine.
Nociceptin/orphanin FQ (N/OFQ),a 17-amino acid neuropeptide,is the endogenous ligand for the nociceptin receptor. Nociceptin acts as a potent anti-analgesic,effectively counteracting the effect of pain-relievers;its activation is associated with brain functions such as pain sensation and fear learning.
The nociceptin opioid peptide receptor (NOP), also known as the nociceptin/orphanin FQ (N/OFQ) receptor or kappa-type 3 opioid receptor,is a protein that in humans is encoded by the OPRL1 gene. The nociceptin receptor is a member of the opioid subfamily of G protein-coupled receptors whose natural ligand is the 17 amino acid neuropeptide known as nociceptin (N/OFQ). This receptor is involved in the regulation of numerous brain activities,particularly instinctive and emotional behaviors. Antagonists targeting NOP are under investigation for their role as treatments for depression and Parkinson's disease,whereas NOP agonists have been shown to act as powerful,non-addictive painkillers in non-human primates.
The urotensin-2 receptor (UR-II-R) also known as GPR14 is a class A rhodopsin family G protein coupled-receptor (GPCR) that is 386 amino acids long which binds primarily to the neuropeptide urotensin II.[1] The receptor quickly rose to prominence when it was found that when activated by urotensin II it induced the most potent vasoconstriction effect ever seen. While the precise function of the urotensin II receptor is not fully known it has been linked to cardiovascular effects,stress,and REM sleep.
The neuropeptide FF receptors are members of the G-protein coupled receptor superfamily of integral membrane proteins which bind the pain modulatory neuropeptides AF and FF. The Neuropeptide FF receptor family is a member of the G protein-coupled receptor superfamily containing two subtypes,NPFF1 and NPFF2,which exhibit a high affinity for Neuropeptide FF (NPFF) peptides. NPFF1 is broadly distributed in the central nervous system with the highest levels found in the limbic system and the hypothalamus. NPFF2 is present in high density,particularly in mammals in the superficial layers of the spinal cord where it is involved in nociception and modulation of opioid functions. These receptors participate to the modulation of opioid receptor function in the brain and spinal cord,and can either reduce or increase opioid receptor function depending which tissue they are released in,reflecting a complex role for neuropeptide FF in pain responses.
Dopamine receptor D1,also known as DRD1. It is one of the two types of D1-like receptor family —receptors D1 and D5. It is a protein that in humans is encoded by the DRD1 gene.
Dopamine receptor D5,also known as D1BR,is a protein that in humans is encoded by the DRD5 gene. It belongs to the D1-like receptor family along with the D1 receptor subtype.
Neuropeptides B/W receptor 1,also known as NPBW1 and GPR7,is a human protein encoded by the NPBWR1 gene. As implied by its name,it and related gene NPBW2 are transmembranes protein that bind Neuropeptide B (NPB) and Neuropeptide W (NPW),both proteins expressed strongly in parts of the brain that regulate stress and fear including the extended amygdala and stria terminalis. When originally discovered in 1995,these receptors had no known ligands and were called GPR7 and GPR8,but at least three groups in the early 2000s independently identified their endogenous ligands,triggering the name change in 2005.
Neuropeptides B/W receptor 2,also known as NPBW2,is a human protein encoded by the NPBWR2 gene.
JTC-801 is an opioid analgesic drug used in scientific research.
NNC 63-0532 is a 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.
J-113,397 is an opioid drug which was the first compound found to be a highly selective antagonist for the nociceptin receptor,also known as the ORL-1 receptor. It is several hundred times selective for the ORL-1 receptor over other opioid receptors,and its effects in animals include preventing the development of tolerance to morphine,the prevention of hyperalgesia induced by intracerebroventricular administration of nociceptin,as well as the stimulation of dopamine release in the striatum,which increases the rewarding effects of cocaine,but may have clinical application in the treatment of Parkinson's disease.
SB-612,111 is an opioid receptor ligand which is a potent and selective antagonist for the nociceptin receptor (ORL-1),several times more potent than the older drug J-113,397. It does not have analgesic effects in its own right,but prevents the development of hyperalgesia,and also shows antidepressant effects in animal studies.
Ro64-6198 is a opioid 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 the other opioid receptors. It produces anxiolytic effects in animal studies equivalent to those of benzodiazepine drugs,but has no anticonvulsant effects and does not produce any overt effects on behaviour. However it does impair short-term memory,and counteracts stress-induced anorexia. It also has antitussive effects,and reduces the rewarding and analgesic effects of morphine,although it did not prevent the development of dependence. It has been shown to reduce alcohol self-administration in animals and suppressed relapses in animal models of alcoholism,and ORL-1 agonists may have application in the treatment of alcoholism.
G-protein-coupled receptor kinase 3 (GRK3) is an enzyme that in humans is encoded by the ADRBK2 gene. GRK3 was initially called Beta-adrenergic receptor kinase 2 (βARK-2),and is a member of the G protein-coupled receptor kinase subfamily of the Ser/Thr protein kinases that is most highly similar to GRK2.
MCOPPB is a drug which acts as a potent and selective agonist for the nociceptin receptor,with a pKi of 10.07 and much weaker activity at other opioid receptors. It has only moderate affinity for the mu opioid receptor,weak affinity for the kappa opioid receptor and negligible binding at the delta opioid receptor. In animal studies,MCOPPB produces potent anxiolytic effects,with no inhibition of memory or motor function,and only slight sedative side effects which do not appear until much higher doses than the effective anxiolytic dose range.
SR-16435 is a drug which acts as a potent partial agonist at both the μ-opioid receptor and nociceptin receptor. In animal studies it was found to be a potent analgesic,with results suggestive of reduced development of tolerance and increased activity against neuropathic pain compared to classic μ-selective agonists.
