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

J Pharmacol Sci. 2006 Jun;101(2):174-8. doi: 10.1254/jphs.scj06001x. Epub 2006 Jun 10.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate Ribose / pharmacology*
  • Animals
  • Calcium / analysis
  • Calcium / metabolism*
  • Cell Line, Tumor
  • Cytosol / metabolism
  • Dose-Response Relationship, Drug
  • Hydrogen Peroxide / pharmacology
  • Insulin-Secreting Cells / drug effects*
  • Insulinoma / metabolism
  • Oxidants / pharmacology
  • Rats
  • TRPM Cation Channels / drug effects*

Substances

  • Oxidants
  • TRPM Cation Channels
  • Adenosine Diphosphate Ribose
  • Hydrogen Peroxide
  • Calcium