effect of tbutyl hydroperoxide on ca2 movement in pc12 pheochromocytoma cells the effect of the oxidant tbutyl hydroperoxide on intracellular free levels of ca2 ca2i in pc12 pheochromocytoma cells was examined by using fura2 as a fluorescent dye tbutyl hydroperoxide induced an increase in ca2i in a concentrationdependent fashion between 50250 microm with an ec50 of 100 microm the ca2i signal consisted of a slow rise and a sustained phase the response was decreased by 65 by removal of extracellular ca2 in ca2free medium pretreatment with 1 microm thapsigargin an endoplasmic reticulum ca2 pump inhibitor abolished 150 microm tbutyl hydroperoxideinduced ca2i increase and conversely pretreatment with tbutyl hydroperoxide abrogated thapsigargininduced ca2i increase the 150 microm tbutyl hydroperoxideinduced ca2i increase in ca2 medium was reduced by 42 5 by pretreatment with 01 microm nicardipine but not by 10 microm verapamil nifedipine nimodipine or diltiazem or by 50 microm la3 or ni2 pretreatment with 10 microm tbutyl hydroperoxide for 40 min did not affect 10 microm atpinduced ca2i increase together the results show that tbutyl hydroperoxide induced significant ca2i increase in pc12 cells by causing store ca2 release from the thapsigarginsensitive endoplasmic reticulum pool in an inositol 145trisphosphateindependent manner and by inducing ca2 influx via a nicardipinesensitive pathway