Can Adding Constitutive Receptor Activity Redefine Biased Signaling Quantification?

2019 ◽  
Vol 40 (3) ◽  
pp. 156-160 ◽  
Author(s):  
Bin Zhou ◽  
David A. Hall ◽  
Jesús Giraldo
Keyword(s):  
Receptor Activity ◽  
Biased Signaling

scholarly journals Biased signaling by endogenous opioid peptides

2020 ◽  
Vol 117 (21) ◽  
pp. 11820-11828 ◽  
Author(s):  
Ivone Gomes ◽  
Salvador Sierra ◽  
Lindsay Lueptow ◽  
Achla Gupta ◽  
Shawn Gouty ◽  
...  
Keyword(s):  
Opioid Receptors ◽  
Cultured Cells ◽  
Opioid Use Disorder ◽  
Receptor Activity ◽  
Prolonged Treatment ◽  
Opioid Use ◽  
Endogenous Opioid System ◽  
Endogenous Opioid ◽  
Biased Signaling ◽  
Brain Slice Preparation

Opioids, such as morphine and fentanyl, are widely used for the treatment of severe pain; however, prolonged treatment with these drugs leads to the development of tolerance and can lead to opioid use disorder. The “Opioid Epidemic” has generated a drive for a deeper understanding of the fundamental signaling mechanisms of opioid receptors. It is generally thought that the three types of opioid receptors (μ, δ, κ) are activated by endogenous peptides derived from three different precursors: Proopiomelanocortin, proenkephalin, and prodynorphin. Posttranslational processing of these precursors generates >20 peptides with opioid receptor activity, leading to a long-standing question of the significance of this repertoire of peptides. Here, we address some aspects of this question using a technical tour de force approach to systematically evaluate ligand binding and signaling properties ([35S]GTPγS binding and β-arrestin recruitment) of 22 peptides at each of the three opioid receptors. We show that nearly all tested peptides are able to activate the three opioid receptors, and many of them exhibit agonist-directed receptor signaling (functional selectivity). Our data also challenge the dogma that shorter forms of β-endorphin do not exhibit receptor activity; we show that they exhibit robust signaling in cultured cells and in an acute brain slice preparation. Collectively, this information lays the groundwork for improved understanding of the endogenous opioid system that will help in developing more effective treatments for pain and addiction.

Role of dorsal and ventral hippocampal muscarinic receptor activity in acquisition and retention of contextual fear conditioning.

2020 ◽  
Vol 134 (5) ◽  
pp. 460-470
Author(s):  
Claudia C. Pinizzotto ◽  
Nicholas A. Heroux ◽  
Colin J. Horgan ◽  
Mark E. Stanton
Keyword(s):  
Fear Conditioning ◽  
Muscarinic Receptor ◽  
Contextual Fear Conditioning ◽  
Receptor Activity ◽  
Contextual Fear

1010-P: Effects of MEDI0382, an Oxyntomodulin-Like Peptide with Targeted GLP-1/Glucagon Receptor Activity, on Amino Acids, Ketones, and Free Fatty Acids

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 1010-P
Author(s):  
VICTORIA E. PARKER ◽  
DARREN ROBERTSON ◽  
TAO WANG ◽  
DAVID C. HORNIGOLD ◽  
MAXIMILIAN G. POSCH ◽  
...  
Keyword(s):  
Amino Acids ◽  
Fatty Acids ◽  
Free Fatty Acids ◽  
Receptor Activity ◽  
Glucagon Receptor
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