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Gen Pharmacol. ;22(5) Multiple opiate receptors of brain and spinal cord in opiate addiction. Bhargava HN(1). Author information: (1)Department of.
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- Opioid receptors.
- How does the opioid system control pain, reward and addictive behavior?
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Chronic administration of opiates to rodents results in the development of tolerance to their pharmacological effects. Physical dependence also develops and is shown by the appearance of abstinence syndrome. Opiates produce their effects by acting on three types of opiate receptors, namely mu, delta and kappa. The qualitative and quantitative aspects of the tolerance-dependence and abstinence symptoms observed after chronic administration of agonists acting at mu-, delta- and kappa-opiate receptors appear to differ.
Tolerance-dependence on mu-opiate agonists, such as morphine, is associated with down-regulation of mu-opiate receptors in spinal cord and specific areas of the brain but delta- and kappa-opiate receptors are unchanged. They are also found in immune system cells.
In the studies of Martin et al. Subsequent studies have shown that naloxone does not act as an antagonist at this receptor [ 28 ]. A sigma receptor that does not display the seven transmembrane domain 7TM structure typical of G protein-coupled receptors has recently been cloned [ 15 ] and shown to be expressed in the nervous system [ 42 ].
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There is also evidence for heterogeneity among sigma receptors. However, the sigma receptors defined to date are no longer regarded as members of the OP receptor family.
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Recently, a zeta receptor gene encoding a protein of aa has been identified, based on the high affinity of the expressed protein for [Met 5 ]enkephalin [ 51 ]. No additional binding affinity measures are available. It is proposed that this receptor regulates cell growth; further work is required to confirm the physiological roles of this protein and its relationship to the OP group of receptors.
The epsilon and lambda receptors have not been cloned or sequenced to date.
The unusual functional properties of the epsilon and lambda receptors might be associated with proteins encoded by non-homologous genes, or with tissue-specific alternative mRNA processing or post-translational modification of the protein products derived from the MOP, DOP, KOP or NOP receptor genes.
Again, there is no evidence suggesting that these subtypes are the products of additional opioid receptor genes. The possible roles of alternative mRNA splicing or post-translational processing remain to be determined.
It is also possible that the cellular environment in which a receptor gene is expressed influences the function of the gene product in a tissue- and stimulus-specific manner. The properties of OP receptors in functioning cells are likely to be determined in part by their recent history of activation and association with other membrane proteins. Recent studies have demonstrated that opioid receptors, like other G protein-coupled receptors, can form functional homo- or heterodimers when co-expressed in cells in culture [ 10 ].
The functional properties of the heterodimeric forms differ significantly from the properties of either monomer form expressed separately [ 18 ].
The potential for the formation of many different forms of OP receptor-protein complexes, possibly varying in prevalence among different cell types, raises the possibility that the each complex may exhibit a unique profile of ligand selectivity and transduction pathway activation. It remains to be determined if the pharmacological evidence for opioid receptor subtypes will eventually be fully or partly explained by the presence of many different forms of OP receptor-membrane protein complexes, including but not limited to OP receptor homo- and heterodimers.
Brain Res. EMBO J. FEBS Lett. Science , : Cvejic S, Devi LA. Classification of opioid receptors. Life Sci. Nature , : Kieffer BL. Mol Pharmacol , 67 : Naunyn Schmiedebergs Arch.
Trends Pharmacol. Cloning, functional expression and localization.
Portoghese PS. Satoh M, Minami M. Terenius L. Acta Pharmacol. To cite this family introduction, please use the following:. Contact us.
How does the opioid system control pain, reward and addictive behavior?
Home Targets G protein-coupled receptors Opioid receptors Introduction. Opioid receptors: Introduction. Nomenclature of opioid receptors The nomenclature for the opioid receptors remains controversial. The opioid receptor family The very well-defined pattern of structure-activity relationships for agonism and antagonism and the absolute stereochemistry requirements for opiate-like analgesic activity induced Beckett and Casy and others to propose receptors for opiate drugs long before the presence of endogenous ligands for these receptors was established [ 1 , 39 ].