Adrenergic Agonists Bind to Adrenergic-Receptor-Like Regions of the Mu Opioid Receptor, Enhancing Morphine and Methionine-Enkephalin Binding: A New Approach to 'Biased Opioids'?
| Autor: | Joerg Labahn, Beth Churchill, Udaya Kumar Tiruttani Subhramanyam, Miah Turke, Robert Root-Bernstein |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Receptors Opioid mu synergy Adrenergic mu opioid receptor Pharmacology allosteric lcsh:Chemistry Mice Methionine 0302 clinical medicine Opioid receptor Receptor lcsh:QH301-705.5 Spectroscopy dimerization Morphine Chemistry General Medicine Adrenergic Agonists Computer Science Applications μ-opioid receptor Histamine Protein Binding medicine.drug Adrenergic receptor medicine.drug_class Enkephalin Methionine Allosteric regulation Article Catalysis norepinephrine receptor dimers Inorganic Chemistry 03 medical and health sciences Receptors Adrenergic alpha-1 ddc:570 Adrenergic antagonist medicine methionine-enkephalin Animals Humans biased opioids Protein Interaction Domains and Motifs epinephrine Amino Acid Sequence Physical and Theoretical Chemistry enhancement Molecular Biology Organic Chemistry Acetylcholine morphine 030104 developmental biology lcsh:Biology (General) lcsh:QD1-999 Opioid Spectrophotometry Ultraviolet 030217 neurology & neurosurgery |
| Zdroj: | International journal of molecular sciences 19(1), 272 (2018). doi:10.3390/ijms19010272 International Journal of Molecular Sciences; Volume 19; Issue 1; Pages: 272 International Journal of Molecular Sciences International Journal of Molecular Sciences, Vol 19, Iss 1, p 272 (2018) |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms19010272 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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