EFFECTS OF EXTRACELLULAR ATP ON FE2-INDUCED CYTOTOXICITY IN PC-12 CELLS()

Extracellular ATP is known to cause a variety of changes, including th e alteration of ion fluxes, cell growth, and other physiological activ ities. Recently, it has been suggested that ATP acts as an excitatory synaptic transmitter, which may produce a Ca2+ influx via the activati on of a P-2y purinoceptor. Rat pheochromocytoma (PC-12) cells are know n to resemble rat sensory neurons and to possess a P-2y purinoceptor. In this study, we demonstrated that extracellular ATP dose-dependently increased PC-12 cell death in the presence of ferrous ions. Voltage-s ensitive calcium channel blockers and calpain and xanthine oxidase inh ibitors were found to be effective at protecting PC-12 cells from Fe2/ATP-induced lipid peroxidation and cell death. These results suggest that xanthine oxidase activation induced by calpains and subsequent fr ee radical formation may be responsible for Fe2+/ATP-induced neuronal cell death.