Biased signaling of G protein coupled receptors (GPCRs): Molecular determinants of GPCR/transducer selectivity and therapeutic potential

2019 ◽  
Vol 200 ◽  
pp. 148-178 ◽  
Author(s):  
Mohammad Seyedabadi ◽  
Mohammad Hossein Ghahremani ◽  
Paul R. Albert
Keyword(s):  
G Protein ◽  
Therapeutic Potential ◽  
G Protein Coupled Receptors ◽  
Molecular Determinants ◽  
Biased Signaling ◽  
G Protein Coupled

G-Protein-Coupled Receptors and Ischemic Stroke: a Focus on Molecular Function and Therapeutic Potential

2021 ◽  
Author(s):  
Zeinab Vahidinia ◽  
Mohammad Taghi Joghataei ◽  
Cordian Beyer ◽  
Mohammad Karimian ◽  
Abolfazl Azami Tameh
Keyword(s):  
Ischemic Stroke ◽  
G Protein ◽  
Therapeutic Potential ◽  
G Protein Coupled Receptors ◽  
Molecular Function ◽  
G Protein Coupled

scholarly journals CB1 Cannabinoid Receptor Signaling and Biased Signaling

Molecules ◽  
2021 ◽  
Vol 26 (17) ◽  
pp. 5413
Author(s):  
Luciana M. Leo ◽  
Mary E. Abood
Keyword(s):  
Adverse Effects ◽  
G Protein ◽  
Conformational Changes ◽  
Cannabinoid Receptor ◽  
Therapeutic Potential ◽  
Receptor Activation ◽  
Cb1 Receptor ◽  
Cb1 Cannabinoid Receptor ◽  
Biased Signaling ◽  
G Protein Coupled

The CB1 cannabinoid receptor is a G-protein coupled receptor highly expressed throughout the central nervous system that is a promising target for the treatment of various disorders, including anxiety, pain, and neurodegeneration. Despite the wide therapeutic potential of CB1, the development of drug candidates is hindered by adverse effects, rapid tolerance development, and abuse potential. Ligands that produce biased signaling—the preferential activation of a signaling transducer in detriment of another—have been proposed as a strategy to dissociate therapeutic and adverse effects for a variety of G-protein coupled receptors. However, biased signaling at the CB1 receptor is poorly understood due to a lack of strongly biased agonists. Here, we review studies that have investigated the biased signaling profile of classical cannabinoid agonists and allosteric ligands, searching for a potential therapeutic advantage of CB1 biased signaling in different pathological states. Agonist and antagonist bound structures of CB1 and proposed mechanisms of action of biased allosteric modulators are used to discuss a putative molecular mechanism for CB1 receptor activation and biased signaling. Current studies suggest that allosteric binding sites on CB1 can be explored to yield biased ligands that favor or hinder conformational changes important for biased signaling.

scholarly journals Seeing cells smell: Dynamic optical measurements of Ca2+ and cAMP signaling from Olfactory Receptors transiently expressed in HEK293TN cells

2019 ◽  
Author(s):  
A Pietraszewska-Bogiel ◽  
L van Weeren ◽  
J Goedhart
Keyword(s):  
G Protein ◽  
Therapeutic Potential ◽  
Olfactory Receptors ◽  
Functional Expression ◽  
G Protein Coupled Receptors ◽  
Optical Measurements ◽  
Camp Signaling ◽  
Kinetic Measurements ◽  
Fluorescent Biosensors ◽  
G Protein Coupled

ABSTRACTOlfactory receptors (ORs) constitute the largest family of G-protein coupled receptors. They are responsible for the perception of odor (olfaction) and also play important roles in other biological processes, including regulation of cell proliferation. Their increasing diagnostic and therapeutic potential, especially for cancer research, requests the ongoing development of methodologies that would allow their robust functional expression in non-olfactory cells, and dynamic analysis of their signaling pathways. To enable realtime detection of OR activity, we use single cell imaging with genetically encoded fluorescent biosensors, Yellow Cameleon or EPAC, which are routinely used for kinetic measurements of Ca2+ or cAMP signaling downstream of various G-protein coupled receptors. We demonstrate that the co-expression of Lucy-Rho tagged variants of ORs together with an accessory protein, RTP1s, in HEK293TN cells is sufficient to detect the activity of a panel of ORs. Using this methodology, we were able to detect both Ca2+ and cAMP signaling downstream of twelve ORs within 2 minutes from the application of odorant.

scholarly journals Molecular determinants of PI3K -mediated activation downstream of G-protein-coupled receptors (GPCRs)

2013 ◽  
Vol 110 (47) ◽  
pp. 18862-18867 ◽  
Author(s):  
O. Vadas ◽  
H. A. Dbouk ◽  
A. Shymanets ◽  
O. Perisic ◽  
J. E. Burke ◽  
...  
Keyword(s):  
G Protein ◽  
G Protein Coupled Receptors ◽  
Molecular Determinants ◽  
G Protein Coupled
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