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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A hominid-specific shift in cerebellar expression, upstream retrotransposons, and a potential cis-regulatory mechanism: bioinformatics analyses of the mu-opioid receptor gene.
TL;DR: Bioinformatic analysis of the OPRM1 upstream region revealed a functional CTCF-binding region that evolved from tandem insertions of retrotransposons L1P1 and L1PA1 upstream (−60 kb) of O PRM1, and the derived G allele became the major allele in the populations represented in the 1000 Genomes Project and may be beneficial.
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Design, synthesis and evaluation of [111In]-labeled, DOTA-conjugated tetrapeptides having high affinity and selectivity for mu opioid receptors
John R. Lever,John R. Lever,Emily A. Fergason-Cantrell,Terry L. Carmack,Lisa D. Watkinson,Fabio Gallazzi +5 more
TL;DR: Visualizing peripheral μ opioid receptors using 111In labeled DOTA-conjugated tetrapeptides appears feasible, but structural modifications to enhance specific binding and metabolic stability, as well as to reduce kidney uptake, will be required.
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Endogenous Opioids and Their Role in Stem Cell Biology and Tissue Rescue
Giovannamaria Petrocelli,Luca Pampanella,Provvidenza Maria Abruzzo,Carlo Ventura,Silvia Canaider,Federica Facchin +5 more
TL;DR: This work focuses on endogenous opioids’ ability to modulate SC proliferation, stress response (to oxidative stress, starvation, or damage following ischemia–reperfusion), and differentiation towards different lineages, such as neurogenesis, vasculogenesis, and cardiogenesis.
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Pharmacogenetics and the postmortem molecular autopsy
Frank R. Wendt,Bruce Budowle +1 more
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