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.
Saeki
M
M
Department of Pharmacology, Faculty of Dentistry, Osaka University, Suita, Japan.
Kamisaki
Y
Y
Maeda
S
S
D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology*; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology; D009566:Nitrates / Q000494:pharmacology*; D010766:Phosphorylation; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism
D009566:Nitrates; C039642:peroxynitric acid; D014443:Tyrosine; C002385:linsidomine; D002217:Carbachol; D008981:Molsidomine; D019833:Genistein; D002118:Calcium