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 perox ynitrite donor, on carbachol-induced increase in intracellular Ca2+ concent ration ([Ca2+](i)) in human neuroblastoma SH-SY5Y cells by means of single cell imaging of [Ca2+](i). SIN-1 potentiated carbachol-induced [Ca2+](i) ri se regardless of external Ca2+, and the potentiation was completely inhibit ed by super oxide dismutase, indicating that peroxynitrite may enhance Ca2 release from intracellular stores. On the other hand, SIN-1 reduced carbac hol-induced inositol 1,4,5-trisphosphate (IP3) formation. Genistein, a tyro sine kinase inhibitor, potentiated carbachol-induced rise of [Ca2+](i) rega rdless of external Ca2+. These results suggest that peroxynitrite may poten tiate the release of Ca2+ from intracellular stores through the perturbatio n of regulation in tyrosine phosphorylation-dephosphorylation system.