scholarly journals Aromatic–Amine Pendants Produce Highly Potent and Efficacious Mixed Efficacy μ-Opioid Receptor (MOR)/δ-Opioid Receptor (DOR) Peptidomimetics with Enhanced Metabolic Stability

2020 ◽  
Vol 63 (4) ◽  
pp. 1671-1683 ◽  
Author(s):  
Sean Henry ◽  
Jessica P. Anand ◽  
Jack J. Twarozynski ◽  
Ashley C. Brinkel ◽  
Irina D. Pogozheva ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Aromatic Amine ◽  
Metabolic Stability ◽  
Μ Opioid Receptor ◽  
Mixed Efficacy ◽  
Δ Opioid Receptor

scholarly journals Opioid Peptidomimetics: Leads for the Design of Bioavailable Mixed Efficacy μ Opioid Receptor (MOR) Agonist/δ Opioid Receptor (DOR) Antagonist Ligands

2013 ◽  
Vol 56 (5) ◽  
pp. 2139-2149 ◽  
Author(s):  
Henry I. Mosberg ◽  
Larisa Yeomans ◽  
Aubrie A. Harland ◽  
Aaron M. Bender ◽  
Katarzyna Sobczyk-Kojiro ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Μ Opioid Receptor ◽  
Mixed Efficacy ◽  
Δ Opioid Receptor

scholarly journals Effects of N-Substitutions on the Tetrahydroquinoline (THQ) Core of Mixed-Efficacy μ-Opioid Receptor (MOR)/δ-Opioid Receptor (DOR) Ligands

2016 ◽  
Vol 59 (10) ◽  
pp. 4985-4998 ◽  
Author(s):  
Aubrie A. Harland ◽  
Aaron M. Bender ◽  
Nicholas W. Griggs ◽  
Chao Gao ◽  
Jessica P. Anand ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Μ Opioid Receptor ◽  
Mixed Efficacy ◽  
Δ Opioid Receptor

scholarly journals Further Optimization and Evaluation of Bioavailable, Mixed-Efficacy μ-Opioid Receptor (MOR) Agonists/δ-Opioid Receptor (DOR) Antagonists: Balancing MOR and DOR Affinities

2015 ◽  
Vol 58 (22) ◽  
pp. 8952-8969 ◽  
Author(s):  
Aubrie A. Harland ◽  
Larisa Yeomans ◽  
Nicholas W. Griggs ◽  
Jessica P. Anand ◽  
Irina D. Pogozheva ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Μ Opioid Receptor ◽  
Mixed Efficacy ◽  
Δ Opioid Receptor

SAR Matrices Enable Discovery of Mixed Efficacy μ-Opioid Receptor Agonist Peptidomimetics with Simplified Structures through an Aromatic-Amine Pharmacophore

2020 ◽  
Vol 12 (1) ◽  
pp. 216-233
Author(s):  
Sean Henry ◽  
Jessica P. Anand ◽  
Ashley C. Brinkel ◽  
Douglas M. McMillan ◽  
Jack. J. Twarozynski ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Aromatic Amine ◽  
Receptor Agonist ◽  
Opioid Receptor Agonist ◽  
Μ Opioid Receptor ◽  
Mixed Efficacy

scholarly journals Proteasome Involvement in Agonist-induced Down-regulation of μ and δ Opioid Receptors

2001 ◽  
Vol 276 (15) ◽  
pp. 12345-12355 ◽  
Author(s):  
Kirti Chaturvedi ◽  
Persis Bandari ◽  
Norihiro Chinen ◽  
Richard D. Howells
Keyword(s):  
Opioid Receptor ◽  
Opioid Receptors ◽  
Proteasome Inhibitors ◽  
Metabolic Labeling ◽  
Down Regulation ◽  
Hek 293 ◽  
293 Cells ◽  
Ubiquitin Proteasome ◽  
Μ Opioid Receptor ◽  
Δ Opioid Receptor

This study investigated the mechanism of agonist-induced opioid receptor down-regulation. Incubation of HEK 293 cells expressing FLAG-tagged δ and μ receptors with agonists caused a time-dependent decrease in opioid receptor levels assayed by immunoblotting. Pulse-chase experiments using [35S]methionine metabolic labeling indicated that the turnover rate of δ receptors was accelerated 5-fold following agonist stimulation. Inactivation of functional Giand Goproteins by pertussis toxin-attenuated down-regulation of the μ opioid receptor, while down-regulation of the δ opioid receptor was unaffected. Pretreatment of cells with inhibitors of lysosomal proteases, calpain, and caspases had little effect on μ and δ opioid receptor down-regulation. In marked contrast, pretreatment with proteasome inhibitors attenuated agonist-induced μ and δ receptor down-regulation. In addition, incubation of cells with proteasome inhibitors in the absence of agonists increased steady-state μ and δ opioid receptor levels. Immunoprecipitation of μ and δ opioid receptors followed by immunoblotting with ubiquitin antibodies suggested that preincubation with proteasome inhibitors promoted accumulation of polyubiquitinated receptors. These data provide evidence that the ubiquitin/proteasome pathway plays a role in agonist-induced down-regulation and basal turnover of opioid receptors.

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