scholarly journals Transforming TRP Channel Drug Discovery Using Medium-Throughput Electrophysiological Assays

2013 ◽  
Vol 19 (3) ◽  
pp. 468-477 ◽  
Author(s):  
Jean-Marie Chambard ◽  
Eric Tagat ◽  
Philippe Boudeau ◽  
Michel Partiseti
Keyword(s):  
Drug Discovery ◽  
Drug Target ◽  
Drug Targets ◽  
Transient Receptor Potential ◽  
Inflammatory Diseases ◽  
Receptor Potential ◽  
Target Class ◽  
Screening Assays ◽  
Transient Receptor ◽  
Almost All

Since the cloning of its first member in 1998, transient receptor potential (TRP) cation channels have become one of the most studied ion channel families in drug discovery. These channels, almost all calcium permeant, have been studied in many different (patho)-physiological and therapeutic areas as diverse as pain; neurodegenerative, cardiovascular, and inflammatory diseases; and cancer. At the same time, implementation of automated electrophysiology screening platforms has significantly increased the tractability of ion channels, mainly voltage gated, as drug targets. The work presented in this article shows the design and validation of TRP screening assays using the IonWorks Quattro platform (Molecular Devices, Sunnyvale, CA), allowing a significant increase in throughput to support drug discovery programs. This new player has a direct impact on resources and timelines by prioritizing potential candidates and reducing the number of molecules requiring final testing by manual patch-clamp, which is still today the gold standard technology for this challenging drug target class.

Transient receptor potential (TRP) channels as potential drug targets in respiratory disease

Cell Calcium ◽  
2003 ◽  
Vol 33 (5-6) ◽  
pp. 551-558 ◽  
Author(s):  
Su Li ◽  
John Westwick ◽  
Chris Poll
Keyword(s):  
Respiratory Disease ◽  
Drug Targets ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Potential Drug ◽  
Transient Receptor ◽  
Potential Drug Targets

Transient Receptor Potential Channels - Emerging Novel Drug Targets for the Treatment of Pain

2013 ◽  
Vol 20 (11) ◽  
pp. 1409-1436 ◽  
Author(s):  
Kinga Salat ◽  
Andrzej Moniczewski ◽  
Tadeusz Librowski
Keyword(s):  
Drug Targets ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
Potential Channels ◽  
Transient Receptor ◽  
Novel Drug ◽  
Novel Drug Targets

scholarly journals TRP Channels as Drug Targets to Relieve Itch

2018 ◽  
Vol 11 (4) ◽  
pp. 100 ◽  
Author(s):  
Zili Xie ◽  
Hongzhen Hu
Keyword(s):  
Drug Targets ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Current Knowledge ◽  
Receptor Potential ◽  
Protective Role ◽  
Chronic Itch ◽  
Transient Receptor

Although acute itch has a protective role by removing irritants to avoid further damage, chronic itch is debilitating, significantly impacting quality of life. Over the past two decades, a considerable amount of stimulating research has been carried out to delineate mechanisms of itch at the molecular, cellular, and circuit levels. There is growing evidence that transient receptor potential (TRP) channels play important roles in itch signaling. The purpose of this review is to summarize our current knowledge about the role of TRP channels in the generation of itch under both physiological and pathological conditions, thereby identifying them as potential drug targets for effective anti-itch therapies.

scholarly journals TRPA1 as a factor and drug target in osteoarthritis: TRPA1 (transient receptor potential ankyrin 1) mediates interleukin-6 expression in chondrocytes

2018 ◽  
Vol 26 ◽  
pp. S124 ◽  
Author(s):  
E. Nummenmaa ◽  
M. Hämäläinen ◽  
A. Pemmari ◽  
L.J. Moilanen ◽  
R.M. Nieminen ◽  
...  
Keyword(s):  
Interleukin 6 ◽  
Drug Target ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor

scholarly journals Inherent P2X7 Receptors Regulate Macrophage Functions during Inflammatory Diseases

2021 ◽  
Vol 23 (1) ◽  
pp. 232
Author(s):  
Wenjing Ren ◽  
Patrizia Rubini ◽  
Yong Tang ◽  
Tobias Engel ◽  
Peter Illes
Keyword(s):  
Transient Receptor Potential ◽  
Inflammatory Diseases ◽  
Second Messengers ◽  
Receptor Potential ◽  
Mononuclear Phagocytes ◽  
P2x7 Receptors ◽  
Pannexin 1 ◽  
Therapeutic Consequences ◽  
High Concentrations ◽  
Transient Receptor

Macrophages are mononuclear phagocytes which derive either from blood-borne monocytes or reside as resident macrophages in peripheral (Kupffer cells of the liver, marginal zone macrophages of the spleen, alveolar macrophages of the lung) and central tissue (microglia). They occur as M1 (pro-inflammatory; classic) or M2 (anti-inflammatory; alternatively activated) phenotypes. Macrophages possess P2X7 receptors (Rs) which respond to high concentrations of extracellular ATP under pathological conditions by allowing the non-selective fluxes of cations (Na+, Ca2+, K+). Activation of P2X7Rs by still higher concentrations of ATP, especially after repetitive agonist application, leads to the opening of membrane pores permeable to ~900 Da molecules. For this effect an interaction of the P2X7R with a range of other membrane channels (e.g., P2X4R, transient receptor potential A1 [TRPA1], pannexin-1 hemichannel, ANO6 chloride channel) is required. Macrophage-localized P2X7Rs have to be co-activated with the lipopolysaccharide-sensitive toll-like receptor 4 (TLR4) in order to induce the formation of the inflammasome 3 (NLRP3), which then activates the pro-interleukin-1β (pro-IL-1β)-degrading caspase-1 to lead to IL-1β release. Moreover, inflammatory diseases (e.g., rheumatoid arthritis, Crohn’s disease, sepsis, etc.) are generated downstream of the P2X7R-induced upregulation of intracellular second messengers (e.g., phospholipase A2, p38 mitogen-activated kinase, and rho G proteins). In conclusion, P2X7Rs at macrophages appear to be important targets to preserve immune homeostasis with possible therapeutic consequences.

Sign in / Sign up

Export Citation Format

Share Document