Genistein inhibits Ca²⁺ influx by extracellular ATP in PC12 pheochromocytoma cells

We previously showed that extracellular ATP-induced Ca²⁺ influx is inhibited by self-activated protein kinase C in rat PC12 pheochromocytoma cells. In the present study, we examined whether tyrosine kinase is involved in the ATP-induced Ca²⁺ influx in PC12 cells. Genistein, an inhibitor of protein tyrosine kinases, which by itself had little effect on ⁴⁵Ca²⁺ influx, significantly suppressed the ATP-induced ⁴⁵Ca²⁺ influx in a dose-dependent manner in the range between 1 and 30 μg/ml. Tyrphostin, another inhibitor of tyrosine kinases chemically distinct from genistein, also inhibited the ⁴⁵Ca²⁺ influx. Sodium orthovanadate, an inhibitor of protein tyrosine phosphatases, markedly enhanced the ATP-induced ⁴⁵Ca²⁺ influx. These results suggest that tyrosine kinase regulates Ca²⁺ influx induced by extracellular ATP in PC12 pheochromocytoma cells.