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dc.contributor.author Tóth, Balázs
dc.contributor.author Iordanov, Iordan
dc.contributor.author Csanády, László
dc.date.accessioned 2016-07-12T06:54:22Z
dc.date.available 2016-07-12T06:54:22Z
dc.date.issued 2015
dc.identifier.citation pagination=419-430; journalVolume=145; journalIssueNumber=5; journalTitle=JOURNAL OF GENERAL PHYSIOLOGY;
dc.identifier.uri http://repo.lib.semmelweis.hu//handle/123456789/2179
dc.identifier.uri doi:10.1085/jgp.201511377
dc.description.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.
dc.relation.ispartof urn:issn:0022-1295
dc.title Ruling out pyridine dinucleotides as true TRPM2 channel activators reveals novel direct agonist ADP-ribose-2'-phosphate
dc.type Journal Article
dc.date.updated 2015-09-29T12:40:56Z
dc.language.rfc3066 en
dc.identifier.mtmt 2949645
dc.identifier.pubmed 25918360
dc.contributor.department SE/AOK/I/Orvosi Biokémiai Intézet
dc.contributor.department SE/AOK/I/OBI/MTA-SE Lendület Ioncsatorna Kutatócsoport
dc.contributor.institution Semmelweis Egyetem
dc.mtmt.swordnote FELTÖLTŐ: Zsárik Judit - judit.zsarik@eok.sote.hu


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