The μ-Opioid Receptor Down-Regulates Differently from the δ-Opioid Receptor: Requirement of a High Affinity Receptor/G Protein Complex Formation

1997 ◽  
Vol 52 (1) ◽  
pp. 105-113 ◽  
Author(s):  
Sumita Chakrabarti ◽  
Wanling Yang ◽  
Ping-Yee Law ◽  
Horace H. Loh
Keyword(s):  
Complex Formation ◽  
G Protein ◽  
Opioid Receptor ◽  
Protein Complex ◽  
High Affinity ◽  
Protein Complex Formation ◽  
High Affinity Receptor ◽  
Μ Opioid Receptor ◽  
Affinity Receptor ◽  
Δ Opioid Receptor

Homodimeric Murine Interleukin-3 Agonists Indicate that Ligand Dimerization is Important for High-Affinity Receptor Complex Formation

1994 ◽  
Vol 10 (1) ◽  
pp. 17-27 ◽  
Author(s):  
Horst Müther ◽  
Klaus Kühlcke ◽  
André Gessner ◽  
Said Abdallah ◽  
Heinz Lother
Keyword(s):  
Complex Formation ◽  
Receptor Complex ◽  
Interleukin 3 ◽  
High Affinity ◽  
High Affinity Receptor ◽  
Affinity Receptor

scholarly journals Structural Insights into the Process of GPCR-G Protein Complex Formation

Cell ◽  
2019 ◽  
Vol 177 (5) ◽  
pp. 1243-1251.e12 ◽  
Author(s):  
Xiangyu Liu ◽  
Xinyu Xu ◽  
Daniel Hilger ◽  
Philipp Aschauer ◽  
Johanna K.S. Tiemann ◽  
...  
Keyword(s):  
Complex Formation ◽  
G Protein ◽  
Protein Complex ◽  
Protein Complex Formation ◽  
Structural Insights

scholarly journals Discovery of μ, δ-Opioid receptor dual biased agonists that overcome the limitation of prior biased agonists

2021 ◽  
Author(s):  
Jin Hee Lee ◽  
Suh-Youn Shon ◽  
Woojin Jeon ◽  
Sung-Jun Hong ◽  
Junsu Ban ◽  
...  
Keyword(s):  
G Protein ◽  
Opioid Receptor ◽  
Opioid Receptors ◽  
Specific Binding ◽  
Binding Modes ◽  
A Cell ◽  
Μ Opioid Receptor ◽  
Δ Opioid Receptor ◽  
Agonistic Effect ◽  
Biased Agonist

ABSTRACTMorphine is widely used to manage pain in patients, although the risk of side effects is significant. The use of biased agonists to the G protein of μ-opioid receptors has been suggested as a potential solution, although Oliceridine and PZM21 have previously failed to demonstrate benefits in clinical studies. An amplification-induced confusion in the process of comparing G protein and beta-arrestin pathways may account for previous biased agonist mis-identification. Here, we have devised a strategy to discover biased agonists with intrinsic efficacy. We computationally simulated 430,000 molecular dockings to the μ-opioid receptor to construct a compound library. Hits were then verified by experiment. Using the verified compounds, we performed simulations to build a second library with a common scaffold, and selected compounds which show biased features to μ and δ-opioid receptors through a cell-based assay. Three compounds (ID110460001, ID110460002, and ID110460003) with a dual biased agonistic effect for μ and δ-opioid receptors were identified. These candidates are full agonists for the μ-opioid receptor, and they show specific binding modes. Based on our findings, we expect our novel compound to act as a biased agonist than conventional drugs such as Oliceridine.

scholarly journals Molecular Determinants of GPCR-G Protein Complex Formation

2012 ◽  
Vol 102 (3) ◽  
pp. 31a-32a
Author(s):  
Tarjani M. Thaker ◽  
Ali I. Kaya ◽  
Anita M. Preininger ◽  
Heidi E. Hamm ◽  
T.M. Iverson
Keyword(s):  
Complex Formation ◽  
G Protein ◽  
Protein Complex ◽  
Protein Complex Formation ◽  
Molecular Determinants

scholarly journals Pathological AT1R-B2R Protein Aggregation and Preeclampsia

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2609
Author(s):  
Ursula Quitterer ◽  
Said AbdAlla
Keyword(s):  
Risk Factors ◽  
Complex Formation ◽  
Protein Aggregation ◽  
G Protein ◽  
Protein Complex ◽  
G Protein Coupled Receptors ◽  
Protein Complex Formation ◽  
The Impact ◽  
G Protein Coupled ◽  
Gpcr Protein

Preeclampsia is one of the most frequent and severe complications of pregnancy. Symptoms of preeclampsia usually occur after 20 weeks of pregnancy and include hypertension and kidney dysfunction with proteinuria. Up to now, delivery of the infant has been the most effective and life-saving treatment to alleviate symptoms of preeclampsia because a causative treatment does not exist, which could prolong a pregnancy complicated with preeclampsia. Preeclampsia is a complex medical condition, which is attributed to a variety of different risk factors and causes. Risk factors account for insufficient placentation and impaired vasculogenesis and finally culminate in this life-threatening condition of pregnancy. Despite progress, many pathomechanisms and causes of preeclampsia are still incompletely understood. In recent years, it was found that excessive protein complex formation between G-protein-coupled receptors is a common sign of preeclampsia. Specifically, the aberrant heteromerization of two vasoactive G-protein-coupled receptors (GPCRs), the angiotensin II AT1 receptor and the bradykinin B2 receptor, is a causative factor of preeclampsia symptoms. Based on this knowledge, inhibition of abnormal GPCR protein complex formation is an experimental treatment approach of preeclampsia. This review summarizes the impact of pathological GPCR protein aggregation on symptoms of preeclampsia and delineates potential new therapeutic targets.

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