Triphenylphosphine Oxide Is a Potent and Selective Inhibitor of the Transient Receptor Potential Melastatin-5 Ion Channel

2010 ◽  
Vol 8 (6) ◽  
pp. 703-713 ◽  
Author(s):  
R. Kyle Palmer ◽  
Karnail Atwal ◽  
Ivona Bakaj ◽  
Stacy Carlucci-Derbyshire ◽  
M. Tulu Buber ◽  
...  
Keyword(s):  
Ion Channel ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Triphenylphosphine Oxide ◽  
Selective Inhibitor ◽  
Transient Receptor Potential Melastatin ◽  
Transient Receptor

scholarly journals Volatile anaesthetics inhibit the thermosensitive nociceptor ion channel transient receptor potential melastatin 3 (TRPM3)

2020 ◽  
Vol 174 ◽  
pp. 113826 ◽  
Author(s):  
Balázs Kelemen ◽  
Erika Lisztes ◽  
Anita Vladár ◽  
Martin Hanyicska ◽  
János Almássy ◽  
...  
Keyword(s):  
Ion Channel ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Volatile Anaesthetics ◽  
Transient Receptor Potential Melastatin ◽  
Transient Receptor

scholarly journals The G protein-biased PZM21 and TRV130 act as partial agonists of μ-opioid receptors signaling to ion channel targets

2018 ◽  
Author(s):  
Yevgen Yudin ◽  
Tibor Rohacs
Keyword(s):  
Ion Channels ◽  
Ion Channel ◽  
G Protein ◽  
Opioid Receptors ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Partial Agonists ◽  
Transient Receptor Potential Melastatin ◽  
Transient Receptor ◽  
Μ Opioid Receptors

Opioids exert many of their acute effects through modulating ion channels via Gβγ subunits. Some of their side effects are attributed to β-arrestin recruitment, and several biased agonists that do not activate this pathway have been developed recently. Here we tested the effects of TRV130, PZM21 and herkinorin, three G-protein biased agonists of μ-opioid receptors (μOR), on ion channel targets. Compared to the full μOR agonist DAMGO, all three biased agonists induced smaller activation of G protein-coupled inwardly rectifying potassium channels (GIRK2), and smaller inhibition of Transient Receptor Potential Melastatin (TRPM3) channels. Furthermore, co-application of TRV130 or PZM21, but not herkinorin reduced the effects of DAMGO on both ion channels. CaV2.2 was also inhibited less by PZM21 and TRV130 than by DAMGO. TRV130, PZM21 and herkinorin were also less effective than DAMGO in inducing dissociation of the Gαi /Gβγ complex. We conclude that TRV130, PZM21 are partial agonists of μOR.

scholarly journals Transient receptor potential melastatin 3 is a phosphoinositide-dependent ion channel

2015 ◽  
Vol 146 (1) ◽  
pp. 65-77 ◽  
Author(s):  
Doreen Badheka ◽  
Istvan Borbiro ◽  
Tibor Rohacs
Keyword(s):  
Ion Channel ◽  
Transient Receptor Potential ◽  
Kinase Inhibitors ◽  
Trp Channels ◽  
Receptor Potential ◽  
Channel Activity ◽  
Intact Cells ◽  
Transient Receptor Potential Melastatin ◽  
Transient Receptor ◽  
Phosphatidylinositol 4

Phosphoinositides are emerging as general regulators of the functionally diverse transient receptor potential (TRP) ion channel family. Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) has been reported to positively regulate many TRP channels, but in several cases phosphoinositide regulation is controversial. TRP melastatin 3 (TRPM3) is a heat-activated ion channel that is also stimulated by chemical agonists, such as pregnenolone sulfate. Here, we used a wide array of approaches to determine the effects of phosphoinositides on TRPM3. We found that channel activity in excised inside-out patches decreased over time (rundown), an attribute of PI(4,5)P2-dependent ion channels. Channel activity could be restored by application of either synthetic dioctanoyl (diC8) or natural arachidonyl stearyl (AASt) PI(4,5)P2. The PI(4,5)P2 precursor phosphatidylinositol 4-phosphate (PI(4)P) was less effective at restoring channel activity. TRPM3 currents were also restored by MgATP, an effect which was inhibited by two different phosphatidylinositol 4-kinase inhibitors, or by pretreatment with a phosphatidylinositol-specific phospholipase C (PI-PLC) enzyme, indicating that MgATP acted by generating phosphoinositides. In intact cells, reduction of PI(4,5)P2 levels by chemically inducible phosphoinositide phosphatases or a voltage-sensitive 5′-phosphatase inhibited channel activity. Activation of PLC via muscarinic receptors also inhibited TRPM3 channel activity. Overall, our data indicate that TRPM3 is a phosphoinositide-dependent ion channel and that decreasing PI(4,5)P2 abundance limits its activity. As all other members of the TRPM family have also been shown to require PI(4,5)P2 for activity, our data establish PI(4,5)P2 as a general positive cofactor of this ion channel subfamily.

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