A Novel Drug Screening Assay for G Protein‐coupled Receptors

2006 ◽  
pp. 51-60 ◽  
Author(s):  
Brian F. O'Dowd ◽  
Xiaodong Ji ◽  
Mohammad Alijaniaram ◽  
Tuan Nguyen ◽  
Susan R. George
Keyword(s):  
G Protein ◽  
Drug Screening ◽  
G Protein Coupled Receptors ◽  
Screening Assay ◽  
Drug Screening Assay ◽  
Novel Drug ◽  
G Protein Coupled

scholarly journals Pharmacological Profile of Brain-derived Neurotrophic Factor (BDNF) Splice Variant Translation Using a Novel Drug Screening Assay

2014 ◽  
Vol 289 (40) ◽  
pp. 27702-27713 ◽  
Author(s):  
Valentina Vaghi ◽  
Alessio Polacchini ◽  
Gabriele Baj ◽  
Vera L. M. Pinheiro ◽  
Annalisa Vicario ◽  
...  
Keyword(s):  
Drug Screening ◽  
Neurotrophic Factor ◽  
Splice Variant ◽  
Brain Derived Neurotrophic Factor ◽  
Pharmacological Profile ◽  
Screening Assay ◽  
Drug Screening Assay ◽  
Novel Drug

Automation and validation of the Transflour technology: a universal screening assay for G protein-coupled receptors

2002 ◽  
Author(s):  
Christine C. Hudson ◽  
Robert H. Oakley ◽  
Rachael D. Cruickshank ◽  
Shay M. Rhem ◽  
Carson R. Loomis
Keyword(s):  
G Protein ◽  
Universal Screening ◽  
G Protein Coupled Receptors ◽  
Screening Assay ◽  
G Protein Coupled

Heterodimers and Receptor Mosaics of Different Types of G-Protein-Coupled Receptors

Physiology ◽  
2008 ◽  
Vol 23 (6) ◽  
pp. 322-332 ◽  
Author(s):  
Kjell Fuxe ◽  
Daniel Marcellino ◽  
Diego Guidolin ◽  
Amina S. Woods ◽  
Luigi F. Agnati
Keyword(s):  
Drug Development ◽  
G Protein ◽  
Research Area ◽  
G Protein Coupled Receptors ◽  
Major Research ◽  
Receptor Mosaics ◽  
Different Types ◽  
Allosteric Mechanisms ◽  
Novel Drug ◽  
G Protein Coupled

Through an assembly of interacting GPCRs, heterodimers and high-order heteromers (termed receptor mosaics) are formed and lead to changes in the agonist recognition, signaling, and trafficking of participating receptors via allosteric mechanisms, sometimes involving the appearance of cooperativity. This field has now become a major research area, and this review deals with their physiology being integrators of receptor signaling in the CNS and their use as targets for novel drug development based on their unique pharmacology.

scholarly journals Metastable GPCR dimers trigger the basal signal by recruiting G-proteins

2020 ◽  
Author(s):  
Rinshi S. Kasai ◽  
Takahiro K. Fujiwara ◽  
Akihiro Kusumi
Keyword(s):  
G Protein ◽  
G Proteins ◽  
Single Molecule ◽  
Resting State ◽  
G Protein Coupled Receptors ◽  
Β2 Adrenergic Receptor ◽  
Low Levels ◽  
Protein Recruitment ◽  
Novel Drug ◽  
G Protein Coupled

G-protein-coupled receptors (GPCRs) constitute the largest family of integral membrane proteins in the human genome and are responsible for various important signaling pathways for vision, olfaction, gustation, emotion, cell migration, etc. A distinct feature of the GPCR-family proteins is that many GPCRs, including the prototypical GPCR, β2-adrenergic receptor (β2AR), elicit low levels of basal constitutive signals without agonist stimulation, which function in normal development and various diseases1–3. However, how the basal signals are induced is hardly known. Another general distinctive feature of GPCRs is to form metastable homo-dimers, with lifetimes on the order of 0.1 s, even in the resting state. Here, our single-molecule-based quantification4 determined the dissociation constant of β2AR homo-dimers in the PM (1.6 ± 0.29 copies/μm2) and their lifetimes (83.2 ± 6.4 ms), and furthermore found that, in the resting state, trimeric G-proteins were recruited to both β2AR monomers and homo-dimers. Importantly, inverse agonists, which suppress the GPCR’s basal constitutive activity, specifically blocked the G-protein recruitment to GPCR homo-dimers, without affecting that to monomers. These results indicate that the G-proteins recruited to transient GPCR homo-dimers are responsible for inducing their basic constitutive signals. These results suggest novel drug development strategies to enhance or suppress GPCR homo-dimer formation.

A novel drug screening assay for papillomavirus specific antiviral activity

1998 ◽  
Vol 37 (2) ◽  
pp. 97-106 ◽  
Author(s):  
Paul R Clark ◽  
M.Luisa Roberts ◽  
Lex M Cowsert
Keyword(s):  
Antiviral Activity ◽  
Drug Screening ◽  
Screening Assay ◽  
Drug Screening Assay ◽  
Novel Drug

scholarly journals Constitutive, Basal, and β-Alanine-Mediated Activation of the Human Mas-Related G Protein-Coupled Receptor D Induces Release of the Inflammatory Cytokine IL-6 and Is Dependent on NF-κB Signaling

2021 ◽  
Vol 22 (24) ◽  
pp. 13254
Author(s):  
Rohit Arora ◽  
Kenny M. Van Theemsche ◽  
Samuel Van Remoortel ◽  
Dirk J. Snyders ◽  
Alain J. Labro ◽  
...  
Keyword(s):  
G Protein ◽  
Inflammatory Mediator ◽  
Dynamic Range ◽  
G Protein Coupled Receptors ◽  
G Protein Coupled Receptor ◽  
Screening Assay ◽  
Cardiovascular Tissue ◽  
Basal Activity ◽  
G Protein Coupled

G protein-coupled receptors (GPCRs) have emerged as key players in regulating (patho)physiological processes, including inflammation. Members of the Mas-related G protein coupled receptors (MRGPRs), a subfamily of GPCRs, are largely expressed by sensory neurons and known to modulate itch and pain. Several members of MRGPRs are also expressed in mast cells, macrophages, and in cardiovascular tissue, linking them to pseudo-allergic drug reactions and suggesting a pivotal role in the cardiovascular system. However, involvement of the human Mas-related G-protein coupled receptor D (MRGPRD) in the regulation of the inflammatory mediator interleukin 6 (IL-6) has not been demonstrated to date. By stimulating human MRGPRD-expressing HeLa cells with the agonist β-alanine, we observed a release of IL-6. β-alanine-induced signaling through MRGPRD was investigated further by probing downstream signaling effectors along the Gαq/Phospholipase C (PLC) pathway, which results in an IkB kinases (IKK)-mediated canonical activation of nuclear factor kappa-B (NF-κB) and stimulation of IL-6 release. This IL-6 release could be blocked by a Gαq inhibitor (YM-254890), an IKK complex inhibitor (IKK-16), and partly by a PLC inhibitor (U-73122). Additionally, we investigated the constitutive (ligand-independent) and basal activity of MRGPRD and concluded that the observed basal activity of MRGPRD is dependent on the presence of fetal bovine serum (FBS) in the culture medium. Consequently, the dynamic range for IL-6 detection as an assay for β-alanine-mediated activation of MRGPRD is substantially increased by culturing the cells in FBS free medium before treatment. Overall, the observation that MRGPRD mediates the release of IL-6 in an in vitro system, hints at a role as an inflammatory mediator and supports the notion that IL-6 can be used as a marker for MRGPRD activation in an in vitro drug screening assay.

Selection of In Silico Drug Screening Results for G-Protein-Coupled Receptors by Using Universal Active Probes

2011 ◽  
Vol 51 (9) ◽  
pp. 2398-2407 ◽  
Author(s):  
Mitsuhito Wada ◽  
Eiji Kanamori ◽  
Haruki Nakamura ◽  
Yoshifumi Fukunishi
Keyword(s):  
G Protein ◽  
Drug Screening ◽  
In Silico ◽  
G Protein Coupled Receptors ◽  
G Protein Coupled ◽  
Selection Of
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