Potentiation of carbachol-induced Ca2+ release by peroxynitrite in human neuroblastoma SH-SY5Y cells.

We have investigated the effect of 3-morpholinosydnonimine (SIN-1), a peroxynitrite donor, on carbachol-induced increase in intracellular Ca2+ concentration ([Ca2+]i) in human neuroblastoma SH-SY5Y cells by means of single cell imaging of [Ca2+]i. SIN-1 potentiated carbachol-induced [Ca2+]i rise regardless of external Ca2+, and the potentiation was completely inhibited by superoxide dismutase, indicating that peroxynitrite may enhance Ca2+ release from intracellular stores. On the other hand, SIN-1 reduced carbachol-induced inositol 1,4,5-trisphosphate (IP3) formation. Genistein, a tyrosine kinase inhibitor, potentiated carbachol-induced rise of [Ca2+]i regardless of external Ca2+. These results suggest that peroxynitrite may potentiate the release of Ca2+ from intracellular stores through the perturbation of regulation in tyrosine phosphorylation-dephosphorylation system.