Extracellular-Added ADP-Ribose Increases Intracellular Free Ca²⁺ Concentration Through Ca²⁺ Release From Stores, but Not Through TRPM2-Mediated Ca²⁺ Entry, in Rat β-Cell Line RIN-5F

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 β-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.