% IMPORTANT: The following is UTF-8 encoded. This means that in the presence % of non-ASCII characters, it will not work with BibTeX 0.99 or older. % Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or % “biber”. @ARTICLE{RootBernstein:842944, author = {Root-Bernstein, Robert and Turke, Miah and Subhramanyam, Udaya and Churchill, Beth and Labahn, Jörg}, title = {{A}drenergic {A}gonists {B}ind to {A}drenergic-{R}eceptor-{L}ike {R}egions of the {M}u {O}pioid {R}eceptor, {E}nhancing {M}orphine and {M}ethionine-{E}nkephalin {B}inding: {A} {N}ew {A}pproach to "{B}iased {O}pioids"?}, journal = {International journal of molecular sciences}, volume = {19}, number = {1}, issn = {1422-0067}, address = {Basel}, publisher = {Molecular Diversity Preservation International}, reportid = {FZJ-2018-01107}, pages = {272}, year = {2018}, abstract = {Extensive 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}, cin = {ICS-6}, ddc = {570}, cid = {I:(DE-Juel1)ICS-6-20110106}, pnm = {551 - Functional Macromolecules and Complexes (POF3-551)}, pid = {G:(DE-HGF)POF3-551}, typ = {PUB:(DE-HGF)16}, UT = {WOS:000424407200266}, pubmed = {pmid:29342106}, doi = {10.3390/ijms19010272}, url = {https://juser.fz-juelich.de/record/842944}, }