Opioid receptor

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.μ2: 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. By the mid-1960s, it had become apparent from pharmacologic studies that opiate drugs were likely to exert their actions at specific receptor sites, and that there were likely to be multiple such sites. Early studies had indicated that opiates appeared to accumulate in the brain. The receptors were first identified as specific molecules through the use of binding studies, in which opiates that had been labeled with radioisotopes were found to bind to brain membrane homogenates. The first such study was published in 1971, using 3H-levorphanol. In 1973, Candace Pert and Solomon H. Snyder published the first detailed binding study of what would turn out to be the μ opioid receptor, using 3H-naloxone. That study has been widely credited as the first definitive finding of an opioid receptor, although two other studies followed shortly after. Purification of the receptor further verified its existence. The first attempt to purify the receptor involved the use of a novel opioid receptor antagonist called chlornaltrexamine that was demonstrated to bind to the opioid receptor. Caruso later purified the detergent-extracted component of rat brain membrane that eluted with the specifically bound 3H-chlornaltrexamine. There are four major subtypes of opioid receptors. OGFr was originally discovered and named as a new opioid receptor zeta (ζ). However it was subsequently found that it shares little sequence similarity with the other opioid receptors, and has quite different function. (I). Name based on order of discovery The opioid receptor family originated from two duplication events of a single ancestral opioid receptor early in vertebrate evolution. Phylogenetic analysis demonstrates that the family of opioid receptors was already present at the origin of jawed vertebrates over 450 million years ago. In humans, this paralogon resulting from a double tetraploidization event resulted in the receptor genes being located on chromosomes 1, 6, 8, and 20. Tetraploidization events often result in the loss of one or more of the duplicated genes, but in this case, nearly all species retain all four opioid receptors, indicating important and specific function. The receptor families delta, kappa, and mu demonstrate 55–58% identity to one another, and a 48–49% homology to the nociceptin receptor. Taken together, this indicates that the NOP receptor gene, OPRL1, has equal evolutionary origin, but a higher mutation rate, than the other receptor genes. The endogenous opioid system is thought to be important in mediating complex social behaviors involved in the formation of stable, emotionally committed relationships. Social attachment was demonstrated to be mediated by the opioid system through experiments administering morphine and naltrexone, an opioid agonist and antagonist, to juvenile guinea pigs. The agonist decreased the preference of the juvenile to be near the mother and reduced distress vocalization whereas the antagonist had the opposite effects. Experiments were corroborated in dogs, chicks, and rats confirming the evolutionary importance of opioid signaling in these behaviors. Researchers have also found that systemic naltrexone treatment of female prairie voles during initial exposure to a male reduced subsequent mating bouts and nonsexual socialization with this familiar partner, when a choice test including a novel male was performed afterwards. This points to a role for opioid receptors in mating behaviors. There is evidence that human-specific opioid-modulated cognitive traits rely not on coding differences for the receptors or ligands, which display 99% homology with primates, but instead are due to regulatory changes in expression levels that are specifically selected for. 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, rendered as the corresponding Greek letter μ. In similar manner, a drug known as ketocyclazocine was first shown to attach itself to 'κ' (kappa) receptors, while the 'δ' (delta) receptor was named after the mouse vas deferens tissue in which the receptor was first characterised. An additional opioid receptor was later identified and cloned based on homology with the cDNA. This receptor is known as the nociceptin receptor or ORL1 (opiate receptor-like 1).