Opioid receptors are a group of G-protein coupled receptors with opioids as ligands. The endogenous opioids are dynorphins, enkephalins and endorphins. The opioid receptors are ~40% identical to somatostatin receptors (SSTRs). In cell biology, G-protein-coupled receptors, also known as GPCR, seven transmembrane receptors, heptahelical receptors, or 7TM receptors, are a class of transmembrane receptors. ... An opioid is any agent that binds to opioid receptors, found principally in the central nervous system and gastrointestinal tract. ... In chemistry, a ligand is an atom, ion, or molecule (see also: functional group) that generally donates one or more of its electrons through a coordinate covalent bond to, or shares its electrons through a covalent bond with, one or more central atoms or ions (these ligands act as a... In an economic model, an endogenous change is one that comes from inside the model and is explained by the model itself. ... An opioid is any agent that binds to opioid receptors found principally in the central nervous system and gastrointestinal tract. ... Dynorphin (Dyn) is a popular and powerful opioid ligand. ... Endorphins are endogenous opioid biochemical compounds. ... Endorphins are endogenous opioid biochemical compounds. ... Somatostatin is a hormone. ... In biochemistry, a receptor is a protein on the cell membrane or within the cytoplasm or cell nucleus that binds to a specific molecule (a ligand), such as a neurotransmitter, hormone, or other substance, and initiates the cellular response to the ligand. ...

Types of receptors

There are three major subtypes of opioid receptors: μ (mu), κ (kappa), and δ (delta). 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 so they converted the 'm' to μ. Similarly a drug known as Ketocyclazocine was first shown to attach itself to kappa receptors [1].An alternative classification system is based on their order of discovery the receptors being termed OP₁ (δ), OP₂ (κ), and OP₃ (μ). In chemistry, a ligand is an atom, ion, or molecule (see also: functional group) that generally donates one or more of its electrons through a coordinate covalent bond to, or shares its electrons through a covalent bond with, one or more central atoms or ions (these ligands act as a... Morphine (INN) (IPA: ) is an extremely powerful opiate analgesic drug and is the principal active agent in opium. ...

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. G-proteins, short for guanine nucleotide binding proteins, are a family of proteins involved in second messenger cascades. ... Binomial name Mus musculus Linnaeus, 1758 Mus musculus is the common house mouse. ... Trinomial name Homo sapiens sapiens Linnaeus, 1758 Humans, or human beings, are bipedal apes belonging to the mammalian species Homo sapiens (Latin for wise man or knowing man) under the family Hominidae (known as the great apes). ...

Separate subtypes (μ₁, μ₂; κ₁, κ₂, κ₃; δ₁, δ₂) 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 (Fries, 2002). Posttranslational modification means the chemical modification of a protein after its translation. ...

The μ-opioid receptor

Mu opioid receptor

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. Hugo is a masculine name. ... The Entrez logo The Entrez Global Query Cross-Database Search System allows access to databases at the National Center for Biotechnology Information (NCBI) website. ... The Mendelian Inheritance in Man project is a database that catalogues all the known diseases with a genetic component, and - when possible - links them to the relevant genes in the human genome. ... The National Center for Biotechnology Information (NCBI) is part of the US National Library of Medicine (NLM), which is a branch of the US National Institutes of Health. ... Swiss-Prot is a curated biological database of protein sequences created in 1986 by Amos Bairoch during his PhD and developed by the Swiss Institute of Bioinformatics and the European Bioinformatics Institute. ... In biology and evolutionary computation, a locus is the position of a gene (or other significant sequence) on a chromosome. ... Chromosome 6 is one of the 23 pairs of chromosomes in humans. ... Hugo is a masculine name. ... The Entrez logo The Entrez Global Query Cross-Database Search System allows access to databases at the National Center for Biotechnology Information (NCBI) website. ... The Mendelian Inheritance in Man project is a database that catalogues all the known diseases with a genetic component, and - when possible - links them to the relevant genes in the human genome. ... The National Center for Biotechnology Information (NCBI) is part of the US National Library of Medicine (NLM), which is a branch of the US National Institutes of Health. ... Swiss-Prot is a curated biological database of protein sequences created in 1986 by Amos Bairoch during his PhD and developed by the Swiss Institute of Bioinformatics and the European Bioinformatics Institute. ... In biology and evolutionary computation, a locus is the position of a gene (or other significant sequence) on a chromosome. ... Chromosome 8 is one of the 23 pairs of chromosomes in humans. ... Hugo is a masculine name. ... The Entrez logo The Entrez Global Query Cross-Database Search System allows access to databases at the National Center for Biotechnology Information (NCBI) website. ... The Mendelian Inheritance in Man project is a database that catalogues all the known diseases with a genetic component, and - when possible - links them to the relevant genes in the human genome. ... The National Center for Biotechnology Information (NCBI) is part of the US National Library of Medicine (NLM), which is a branch of the US National Institutes of Health. ... Swiss-Prot is a curated biological database of protein sequences created in 1986 by Amos Bairoch during his PhD and developed by the Swiss Institute of Bioinformatics and the European Bioinformatics Institute. ... In biology and evolutionary computation, a locus is the position of a gene (or other significant sequence) on a chromosome. ... Chromosome 1 is, by convention, the designation for the largest human chromosome. ... Hugo is a masculine name. ... The Entrez logo The Entrez Global Query Cross-Database Search System allows access to databases at the National Center for Biotechnology Information (NCBI) website. ... The Mendelian Inheritance in Man project is a database that catalogues all the known diseases with a genetic component, and - when possible - links them to the relevant genes in the human genome. ... The National Center for Biotechnology Information (NCBI) is part of the US National Library of Medicine (NLM), which is a branch of the US National Institutes of Health. ... Swiss-Prot is a curated biological database of protein sequences created in 1986 by Amos Bairoch during his PhD and developed by the Swiss Institute of Bioinformatics and the European Bioinformatics Institute. ... In biology and evolutionary computation, a locus is the position of a gene (or other significant sequence) on a chromosome. ... Chromosome 9 is one of the 23 pairs of chromosomes in humans. ... Image File history File links Mu_opioid_receptor. ... Image File history File links Mu_opioid_receptor. ...

The μ-receptors exist mostly presynaptically in the periaqueductal gray region, and in the superficial dorsal horn of the spinal cord. 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. In a synapse between two neurons, the cell that releases the neurotransmitter is referred to as the presynaptic cell. ... The Spinal cord nested in the vertebral column. ... Vesalius Fabrica, 1543. ... The nucleus accumbens (also known as the accumbens nucleus or nucleus accumbens septi) is a collection of neurons located where the head of the caudate and the anterior portion of the putamen meet just lateral to the septum pellucidum. ... In neuroanatomy, a nucleus is a central nervous system structure that is composed mainly of gray matter, and which acts as a hub or transit point for electrical signals in a single neural subsystem. ... This article or section does not cite its references or sources. ... Diagram of Ephedrine An alkaloid is a nitrogenous organic molecule that has a pharmacological effect on humans and animals. ...

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 developes 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 [3]. For other uses of painkiller, see painkiller (disambiguation) An analgesic (colloquially known as painkiller) is any member of the diverse group of drugs used to relieve pain. ...

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. In pharmacology, an inverse agonist is an agent which binds to the same receptor binding-site as an agonist for that receptor but exerts the opposite pharmacological effect. ...

The κ-opioid receptor

κ-Opioid receptors are also involved with analgesia, but activation also produces marked nausea and dysphoria. Kappa ligands are also known for their characteristic diuretic effects, due to their negative regulation of anti diuretic hormone(ADH). Kappa agonism is neuroprotective against hypoxiaischemia, as such, kappa receptors may represent a novel therapeutic target. The endogenous ligands for the Kappa receptor are the dynorphins. κ receptors are located in the periphery by pain neurons, in the spinal cord and in the brain. Kappa agonists whether full or partial produce psychotomimetic effects. In the case of the mixed (partial) agonist/antagonist analgesic drugs e.g. butorphanol, nalbuphine and buprenorphine the psychotomimesis is undesirable and serves to limit abuse potential. In the case of Salvinorin A, a structuraly novel neoclerodane diterpene Kappa ligand, these effects are sought after. While Salvinorin A is considered a hallucinogen by those to whom it is known, its effects are qualitatively different than those produced by the classical indoleamine hallucinogens. [4]. Look up dysphoria in Wiktionary, the free dictionary. ... Butorphanol (INN) is a morphinan-type synthetic opioid analgesic marketed in the US under the trade name Stadol. ... Nalbuphine (nalbuphine hydrochloride) is a synthetic opioid used commercially as an analgesic under a variety of trade names, including Nubain. ... Buprenorphine, also colloquially referred to as bupe, is an opioid drug with partial agonist and antagonist actions. ... Salvinorin A is the main active psychotropic constituent of the plant Salvia divinorum (diviners sage, Mexican mint). ...

The δ-opioid receptor

δ-Opioid receptor activation also produces analgesia. Some research suggests that they may also be related to seizures. The endogenous ligands for the δ receptor are the enkephalins. Until quite recently, there were few pharmacological tools for the study of δ receptors. As a consequence, our understanding of their function is much more limited than those of the other opioid receptors.

Recent work indicates that exogenous ligands which activate the delta receptors mimic the phenomenon known as 'ischemic preconditioning'. Experimentally, if short periods of transient ischemia are induced the downstream tissues are robustly protected if permanent interruption of the blood supply is then effected. Opiates and opioids with delta activity mimic this effect. In the rat model introduction of delta active ligands results in significant cardioprotection.

The σ receptor

Schematic σ opioid receptor

The sigma receptors σ₁ and σ₂ were once thought to be a type of opioid receptor, because the d stereoisomers of the benzomorphan class of opioid drugs had no effects at μ, κ, and δ receptors, but reduced coughing. However, pharmacological testing indicated that the sigma receptors were activated by drugs completely unrelated to the opioids, and their function was unrelated to the function of the opioid receptors. For example, phencyclidine (PCP), and the antipsychotic haloperidol may interact with these receptors. Neither phencyclidine nor haloperidol have any appreciable chemical similarity to the opioids. When the σ₁ receptor was isolated and cloned, it was found to have no structural similarity to the opioid receptors. At this point, they were designated as a separate class of receptors. The functions of these receptors are poorly understood and any endogenous ligands have yet to be identified. Image File history File links Sigma_opioid_receptor. ... Image File history File links Sigma_opioid_receptor. ...

The orphan opioid receptor (ORL 1)

An additional opioid receptor has been identified and cloned based on homology with the cDNA. This receptor is known as the ORL 1 receptor. Its natural ligand is known alternately as nociceptin or orphanin. Nociceptin is thought to be an endogenous antagonist of dopamine transport that may act either directly on dopamine or by inhibiting GABA to effect dopamine levels [5]. Within the central nervous system its action can be either similar or opposite to those of opioids depending on their location [6]. 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[7]. In genetics, complementary DNA (cDNA) is single-stranded DNA synthesized from a mature mRNA template. ... This article or section is in need of attention from an expert on the subject. ... Gaba may refer to: Gabâ or gabaa (Philippines), the concept of negative karma of the Cebuano people GABA, the gamma-amino-butyric acid neurotransmitter GABA receptor, in biology, receptors with GABA as their endogenous ligand Gaba 1 to 1, an English conversational school in Japan Marianne Gaba, a US model... A diagram showing the CNS: 1. ... Pain is both a sensory and emotional experience, generally associated tissue damage, or inflammation. ... In psychology, memory is the ability of an organism to store, retain, and subsequently recall information. ... The circulatory system or cardiovascular system is the organ system which circulates blood around the body of most animals. ... Kidneys viewed from behind with spine removed The kidneys are bean-shaped excretory organs in vertebrates. ... Locomotor activity (LMA) refers to the movement from place to place. ... For the Physics term GUT, please refer to Grand unification theory The gastrointestinal or digestive tract, also referred to as the GI tract or the alimentary canal or the gut, is the system of organs within multicellular animals which takes in food, digests it to extract energy and nutrients, and... Anxiety is an unpleasant complex combination of emotions that includes fear, apprehension and worry, and is often accompanied by physical sensations such as palpitations, nausea, chest pain and/or shortness of breath. ... Chemical structure of D-Aspartic Acid, a common Amino Acid neurotransmitter. ...

ORL 1 agonists are being studied as treatments for heart failure and migraine [8] while nociceptin antagonists may have antidepressant qualities [9]. The novel drug buprenorphine is a partial agonist at ORL 1 receptors while its metabolite norbuprenorphine is a full agonist at these receptors [10]. Agonists An agonist is a substance that binds to a receptor and triggers a response by the cell. ... This article refers to literary antagonists. ... Buprenorphine, also colloquially referred to as bupe, is an opioid drug with partial agonist and antagonist actions. ... Buprenorphine, also colloquially referred to as bupe, is an opioid drug with partial agonist and antagonist actions. ...

References

• 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
• 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.
• Henderson G, McKnight AT (1997). The orphan opioid receptor and its endogenous ligand - nociceptin/orphanin FQ. Trends Pharmacol Sci 18, 293-300.

See also

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

Naloxone is a drug used to counter the effects of overdosing on opioids such as heroin and morphine. ...

External links

• IUPHAR GPCR Database - Opioid Receptors