Dual action of palmitoyl trifluoromethyl ketone (PACOCF3) on Ca2+ signaling:: activation of extracellular Ca2+ influx and alteration of ATP- and bradykinin-induced Ca2+ responses in Madin-Darby canine kidney cells

The effect Of the phospholipase A(2) inhibitor palmitoyl trifluoromethyl ketone (PACOCF(3)) on Ca2+ signaling in Madin Darby canine kidney (MDCK) cells was examined using fura-2 as the fluorescent Ca2+ indicator. At a concentration of 20 muM, PACOCF(3) did not change basal cytosolic free calcium concentrations ([Ca2+](i)), but at concentrations of 50 250 muM PACOCF(3) induced an increase in [Ca2+](i) by activating extracellular Ca2+ entry which was partly suppressed by 50 muM La3+. The effect of PACOCF(3) was abolished by removal of extracellular Ca2+ PACOCF(3) (10 muM) enhanced both the peak value and the al-ea under the curve of the [Ca2+](i) increase induced by 10 muM ATP and 1 muM bradykinin by potentiating extracellular Ca2+ influx without affecting internal Ca2+ release. Several other phospholipase A(2) inhibitors had no effect on basal [Ca2+](i) or agonist-induced [Ca2+](i) increases. Collectively, the results suggest that PACOCF(3) alters Ca2+ signaling in renal tubular cells in a manner independent of phospholipase A(2) inhibition.