Evidence map›Paper›PMID 25918360›Full record

ArticleThe Journal of general physiology2015

Ruling out pyridine dinucleotides as true TRPM2 channel activators reveals novel direct agonist ADP-ribose-2'-phosphate.

Balázs Tóth, Iordan Iordanov, László Csanády

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of general physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
8.1field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

42 citing papers in PubMed, 67 citations in OpenAlex.

  1. Article
  2. Review
  3. [Advances in the development of transient receptor potential melastatin 2 channel inhibitors].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2025
    Review
  4. Article
  5. A conserved mechanism couples cytosolic domain movements to pore gating in the TRPM2 channel.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  6. Review
  7. NADAntioxidants & redox signaling · 2023
    Review
  8. Article
  9. Review
  10. Hyperthermia and Serotonin: The Quest for a "Better Cyproheptadine".International journal of molecular sciences · 2022
    Review
  11. Article
  12. The Role of TRPM2 in Endothelial Function and Dysfunction.International journal of molecular sciences · 2021
    Review
  13. Review
  14. Roles of NADMolecules (Basel, Switzerland) · 2020
    Review
  15. Review
  16. Review
  17. Article
  18. Review
  19. Article
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

Balázs TóthDepartment of Medical Biochemistry and MTA-SE Ion Channel Research Group, Semmelweis University, Budapest H-1094, Hungary Department of Medical Biochemistry and MTA-SE Ion Channel Research Group, Semmelweis University, Budapest H-1094, Hungary.
Iordan IordanovDepartment of Medical Biochemistry and MTA-SE Ion Channel Research Group, Semmelweis University, Budapest H-1094, Hungary Department of Medical Biochemistry and MTA-SE Ion Channel Research Group, Semmelweis University, Budapest H-1094, Hungary.
László CsanádyDepartment of Medical Biochemistry and MTA-SE Ion Channel Research Group, Semmelweis University, Budapest H-1094, Hungary Department of Medical Biochemistry and MTA-SE Ion Channel Research Group, Semmelweis University, Budapest H-1094, Hungary csanay.laszlo@med.semmelweis-univ.hu.
Semmelweis University · HU

Funding

Howard Hughes Medical Institute
6 · The paper itself

Abstract

Transient receptor potential melastatin 2 (TRPM2), a Ca(2+)-permeable cation channel implicated in postischemic neuronal cell death, leukocyte activation, and insulin secretion, is activated by intracellular ADP ribose (ADPR). In addition, the pyridine dinucleotides nicotinamide-adenine-dinucleotide (NAD), nicotinic acid-adenine-dinucleotide (NAAD), and NAAD-2'-phosphate (NAADP) have been shown to activate TRPM2, or to enhance its activation by ADPR, when dialyzed into cells. The precise subset of nucleotides that act directly on the TRPM2 protein, however, is unknown. Here, we use a heterologously expressed, affinity-purified-specific ADPR hydrolase to purify commercial preparations of pyridine dinucleotides from substantial contaminations by ADPR or ADPR-2'-phosphate (ADPRP). Direct application of purified NAD, NAAD, or NAADP to the cytosolic face of TRPM2 channels in inside-out patches demonstrated that none of them stimulates gating, or affects channel activation by ADPR, indicating that none of these dinucleotides directly binds to TRPM2. Instead, our experiments identify for the first time ADPRP as a true direct TRPM2 agonist of potential biological interest.

Indexed as

Ion Channel GatingAdenosine Diphosphate RiboseAnimalsHumansNADNADPProtein BindingPyrophosphatasesTRPM Cation ChannelsXenopusAdenosine Diphosphate RiboseNAADPNADNADPNUDT9PyrophosphatasesTRPM2 protein, humanTRPM Cation Channels

Identifiers

PMID25918360
PMCPMC4411260
OpenAlexW2110027591

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.