Extracellular-added ADP-ribose increases intracellular free Ca2+ concentration through Ca2+ release from stores, but not through TRPM2-mediated Ca2+ entry, in rat beta-cell line RIN-5F.
Intracellular ADP-ribose is an activator of TRPM2, which is a Ca2+-permeable channel and mediates H2O2-induced cell death, in the TRPM2-expressing rat beta-cell line RIN-5F. We examined the effect of extracellular-added ADP-ribose on intracellular Ca2+ concentration in RIN-5F cells. ADP-ribose induced Ca2+ release from the thapsigargin-sensitive Ca2+ store, but not Ca2+ entry across the plasma membrane. A phospholipase C (PLC) inhibitor and a non-specific IP3 receptor inhibitor blocked its Ca2+ release. H2O2-induced Ca2+ entry through TRPM2 was not affected by extracellular ADP-ribose. These findings suggest that extracellular-added ADP-ribose induces Ca2+ release through the PLC-IP3 pathway and does not act as a TRPM2 activator.
Ishii
Masakazu
M
Department of Pathophysiology, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan. masakazu@pharm.showa-u.ac.jp
Shimizu
Shunichi
S
Hagiwara
Tamio
T
Wajima
Teruaki
T
Miyazaki
Akira
A
Mori
Yasuo
Y
Kiuchi
Yuji
Y
D000246:Adenosine Diphosphate Ribose / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000032:analysis / Q000378:metabolism*; D045744:Cell Line, Tumor; D003600:Cytosol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006861:Hydrogen Peroxide / Q000494:pharmacology; D050417:Insulin-Secreting Cells / Q000187:drug effects*; D007340:Insulinoma / Q000378:metabolism; D016877:Oxidants / Q000494:pharmacology; D051381:Rats; D050053:TRPM Cation Channels / Q000187:drug effects*
D016877:Oxidants; D050053:TRPM Cation Channels; D000246:Adenosine Diphosphate Ribose; D006861:Hydrogen Peroxide; D002118:Calcium