Activators of TRPM2: Getting it right

Rosenbaum, Tamara

doi:10.1085/jgp.201511405

Cited by 7 publications

(7 citation statements)

References 21 publications

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“…oxidative stress. Reversible ribosylation of the TRPM2 protein opens calcium channels and induces a cation current [ 12 , 13 , 14 ]. Kheradpezhouh et al, 2014 presented data suggesting that exposure of hepatocytes to acetaminophen (N-acetyl-p-aminophenol; paracetamol), results in activation of TRPM2 channels and induces a cation current similar to that activated by oxidative stress (hydrogen peroxide; H 2 O 2 ) or the intracellular application of ADP-ribose [ 15 ].…”

Section: Trpm2-activatorsmentioning

confidence: 99%

Hyperthermia and Serotonin: The Quest for a “Better Cyproheptadine”

Petroianu

2022

IJMS

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Fine temperature control is essential in homeothermic animals. Both hyper- and hypothermia can have deleterious effects. Multiple, efficient and partly redundant mechanisms of adjusting the body temperature to the value set by the internal thermostat exist. The neural circuitry of temperature control and the neurotransmitters involved are reviewed. The GABAergic inhibitory output from the brain thermostat in the preoptic area POA to subaltern neural circuitry of temperature control (Nucleus Raphe Dorsalis and Nucleus Raphe Pallidus) is a function of the balance between the (opposite) effects mediated by the transient receptor potential receptor TRPM2 and EP3 prostaglandin receptors. Activation of TRPM2-expressing neurons in POA favors hypothermia, while inhibition has the opposite effect. Conversely, EP3 receptors induce elevation in body temperature. Activation of EP3-expressing neurons in POA results in hyperthermia, while inhibition has the opposite effect. Agonists at TRPM2 and/or antagonists at EP3 could be beneficial in hyperthermia control. Activity of the neural circuitry of temperature control is modulated by a variety of 5-HT receptors. Based on the theoretical model presented the “ideal” antidote against serotonin syndrome hyperthermia appears to be an antagonist at the 5-HT receptor subtypes 2, 4 and 6 and an agonist at the receptor subtypes 1, 3 and 7. Very broadly speaking, such a profile translates in a sympatholytic effect. While a compound with such an ideal profile is presently not available, better matches than the conventional antidote cyproheptadine (used off-label in severe serotonin syndrome cases) appear to be possible and need to be identified.

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Section: Trpm2-activatorsmentioning

confidence: 99%

Hyperthermia and Serotonin: The Quest for a “Better Cyproheptadine”

Petroianu

2022

IJMS

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“…Cyclic ADPR is an activator of the ryanodine receptor (RyR) calcium channel, able to trigger Ca 2+ flow from the endoplasmic reticulum to the cytosol . ADPR is the only known activator of the transient receptor potential melastatin 2 calcium channel (TRPM2) . TRPM2 channels are situated in the cytoplasmic membrane and transport Ca 2+ from the cell exterior to the cytoplasm.…”

Section: Evidence Supporting Cd38‐mediated Pathogenesis In Hiv Diseasementioning

confidence: 99%

“…[104] ADPR is the only known activator of the transient receptor potential melastatin 2 calcium channel (TRPM2). [105] TRPM2 channels are situated in the cytoplasmic membrane and transport Ca 2+ from the cell exterior to the cytoplasm. ADPR and cADPR act intracellularly, which also raises the question of whether and how CD38, with its catalytic site facing outside the cell, can increase cADPR and ADPR concentrations in the cytoplasm.…”

Section: Evidence Supporting Cd38-mediated Pathogenesis In Hiv Diseasementioning

confidence: 99%

HIV Disease Progression: Overexpression of the Ectoenzyme CD38 as a Contributory Factor?

et al. 2018

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Summary Despite abundant evidence associating CD38 overexpression and CD4 T cell depletion in HIV infection, no causal relation has been investigated. To address this issue, we propose a series of mechanisms, supported by evidence from different fields, by which CD38 overexpression could facilitate CD4 T cell depletion in HIV infection. According to our model, increased catalytic activity of CD38 may reduce CD4 T cells’ cytoplasmic nicotinamide adenine dinucleotide (NAD), leading to a chronic Warburg effect. This would reduce mitochondrial function. Simultaneously, CD38’s catalytic products ADPR and cADPR may be transported to the cytoplasm, where they can activate calcium channels and increase cytoplasmic Ca2+ concentrations, further altering mitochondrial integrity. These mechanisms would decrease the viability and regenerative capacity of CD4 T cells. These hypotheses can be tested experimentally, and might reveal novel therapeutic targets.

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“…Stable ADPR analogues may also be useful when clarication of the precise second messenger that is acting under physiological conditions has proved challenging. 9,10 Small changes to the structure of ADPR have demonstrated profound effects on activity and, as a result, synthetic analogues closely based on the ADPR structure have been very informative. [11][12][13] Analogues with modications in the adenosine 11,13 and terminal ribose [14][15][16][17] motifs have been prepared via coupling of a modied 5 0 -O-phosphoryl adenosine or ribose to its 5 0 -Ophosphoryl counterpart using morpholidate, diphenylphosphonate or imidazolide methods to activate one phosphate towards nucleophilic attack and thus generate the pyrophosphate.…”

Section: Introductionmentioning

confidence: 99%

“…Neither compound reduced the TRPM2 current significantly when compared to the control (pipette solution containing only ADPR). The numbers at the bottom indicate the number of cells analysed.1780 | RSC Adv., 2020,10,[1776][1777][1778][1779][1780][1781][1782][1783][1784][1785] This journal is © The Royal Society of Chemistry 2020RSC Advances PaperOpen Access Article. Published on 09 January 2020.…”

mentioning

confidence: 99%