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000842944 1001_ $$0P:(DE-HGF)0$$aRoot-Bernstein, Robert$$b0$$eCorresponding author
000842944 245__ $$aAdrenergic Agonists Bind to Adrenergic-Receptor-Like Regions of the Mu Opioid Receptor, Enhancing Morphine and Methionine-Enkephalin Binding: A New Approach to "Biased Opioids"?
000842944 260__ $$aBasel$$bMolecular Diversity Preservation International$$c2018
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000842944 520__ $$aExtensive evidence demonstrates functional interactions between the adrenergic and opioid systems in a diversity of tissues and organs. While some effects are due to receptor and second messenger cross-talk, recent research has revealed an extracellular, allosteric opioid binding site on adrenergic receptors that enhances adrenergic activity and its duration. The present research addresses whether opioid receptors may have an equivalent extracellular, allosteric adrenergic binding site that has similar enhancing effects on opioid binding. Comparison of adrenergic and opioid receptor sequences revealed that these receptors share very significant regions of similarity, particularly in some of the extracellular and transmembrane regions associated with adrenergic binding in the adrenergic receptors. Five of these shared regions from the mu opioid receptor (muOPR) were synthesized as peptides and tested for binding to adrenergic, opioid and control compounds using ultraviolet spectroscopy. Adrenergic compounds bound to several of these muOPR peptides with low micromolar affinity while acetylcholine, histamine and various adrenergic antagonists did not. Similar studies were then conducted with purified, intact muOPR with similar results. Combinations of epinephrine with methionine enkephalin or morphine increased the binding of both by about half a log unit. These results suggest that muOPR may be allosterically enhanced by adrenergic agonists. View Full-Text Keywords:   biased opioids; morphine; methionine-enkephalin; epinephrine; norepinephrine; enhancement; synergy; allosteric; mu opioid receptor; receptor dimers; dimerization
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000842944 7001_ $$0P:(DE-HGF)0$$aTurke, Miah$$b1
000842944 7001_ $$0P:(DE-HGF)0$$aSubhramanyam, Udaya$$b2
000842944 7001_ $$0P:(DE-HGF)0$$aChurchill, Beth$$b3
000842944 7001_ $$0P:(DE-Juel1)131973$$aLabahn, Jörg$$b4$$ufzj
000842944 773__ $$0PERI:(DE-600)2019364-6$$a10.3390/ijms19010272$$gVol. 19, no. 1, p. 272 -$$n1$$p272 $$tInternational journal of molecular sciences$$v19$$x1422-0067$$y2018
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