Mu Opioids and Their Receptors: Evolution of a Concept
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TLDR
Understanding of these morphine-like agents and their receptors has undergone an evolution in thinking over the past 35 years, which now reveals a complexity of the morphine- like agents andtheir receptors that had not been previously appreciated.Abstract:
Opiates are among the oldest medications available to manage a number of medical problems. Although pain is the current focus, early use initially focused upon the treatment of dysentery. Opium contains high concentrations of both morphine and codeine, along with thebaine, which is used in the synthesis of a number of semisynthetic opioid analgesics. Thus, it is not surprising that new agents were initially based upon the morphine scaffold. The concept of multiple opioid receptors was first suggested almost 50 years ago (Martin, 1967), opening the possibility of new classes of drugs, but the morphine-like agents have remained the mainstay in the medical management of pain. Termed mu, our understanding of these morphine-like agents and their receptors has undergone an evolution in thinking over the past 35 years. Early pharmacological studies identified three major classes of receptors, helped by the discovery of endogenous opioid peptides and receptor subtypes—primarily through the synthesis of novel agents. These chemical biologic approaches were then eclipsed by the molecular biology revolution, which now reveals a complexity of the morphine-like agents and their receptors that had not been previously appreciated.read more
Citations
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References
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Journal ArticleDOI
Morphine in cow and human milk: could dietary morphine constitute a ligand for specific morphine (mu) receptors?
Eli Hazum,Julie J. Sabatka,Kwen-Jen Chang,David A. Brent,John W. A. Findlay,Pedro Cuatrecasas +5 more
TL;DR: Morphine has been found in cow and human milk at concentrations of 200 to 500 nanograms per liter, and since morphine-like materials have been described in brain and intestine, it is possible that morphine in food may be the source of this material and a normal ligand specific for mu receptors.
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Opiate, enkephalin, and endorphin analgesia Relations to a single subpopulation of opiate receptors
TL;DR: These studies suggest that both opiate and opioid peptide analgesia is mediated through a single receptor subpopulation distinct from those involved with respiratory depression, and raise the possibility of specific opiate analgesics without respiratory depression.
Journal ArticleDOI
Epigenetic programming of μ‐opioid receptor gene in mouse brain is regulated by MeCP2 and brg1 chromatin remodelling factor
Cheol Kyu Hwang,Kyu Young Song,Chun Sung Kim,Hack Sun Choi,Xiao Hong Guo,Ping-Yee Law,Li Na Wei,Horace H. Loh +7 more
TL;DR: It is concluded that MOR gene expression is epigenetically programmed in various brain regions and that MeCP2 assists the epigenetic program during DNA methylation and chromatin remodelling of the MOR promoter.
Journal ArticleDOI
Transcriptional and Epigenetic Regulation of Opioid Receptor Genes: Present and Future
Li Na Wei,Horace H. Loh +1 more
TL;DR: Regulation of KOR expression is distinctly complex, and KOR exerts a unique function in neurite extension, indicating that KOR is not simply a pharmacological cousin of MOR and DOR, as the expression of OR proteins is ultimately controlled by extensive posttranscriptional processing.
Journal ArticleDOI
Autoradiographic localization of kappa opiate receptors to deep layers of the cerebral cortex may explain unique sedative and analgesic effects
TL;DR: The highest density and most selective localization of putative kappa receptors occurs in layers V and VI of the cerebral cortex, which may account for the unique sedative and analgesic actions of kappa opiates.
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