DUAL EFFECTS OF MASTOPARAN ON INTRACELLULAR FREE CA2+ CONCENTRATIONS IN HUMAN ASTROCYTOMA-CELLS

1 The effect of mastoparan, a wasp venom toxin, on intracellular free Ca2+ concentration ([Ca2+](i)) was examined in human astrocytoma cells. Mastoparan inhibited [Ca2+](i) induced by carbachol (100 mu M) in a concentration-dependent manner in the absence of extracellular Ca2+, consistent with our previous result:s showing that mastoparan inhibits phosphoinositide hydrolysis in human astrocytoma cells. 2 In contrast, mastoparan itself increased [Ca2+](i) and augmented carbachol-induced increase in the [Ca2+](i) in the presence of extracellular Ca2+, suggesting that mastoparan elicited Ca2+ influx from the extracellular medium. The increase appeared to be maximum at extracellular Ca2+ concentrations of 0.1-0.2mM. The higher concentrations of extracellular Ca2+ depressed the influx. 3 Pertussis toxin did not affect mastoparan-induced inhibition of [Ca2+](i) in the absence of extracellular Ca2+, consistent with the previous results that pertussis toxin did not affect mastoparan-induced inhibition of phosphoinositide hydrolysis. 4 Pertussis toxin augmented mastoparan-induced increase in [Ca2+](i) in the presence of extracellular Ca2+, suggesting that pertussis toxin substrate(s) seems to be inhibitory for Ca2+ influx induced by mastoparan. 5 Verapamil, nifedipine and diltiazem (each 10 mu M), L-type Ca2+ antagonists, did not affect mastoparan-induced Ca2+ influx. However, verapamil (10 mu M) slightly inhibited the increase in [Ca2+](i) induced by carbachol in the presence of mastoparan. 6 The results obtained in the present study indicate that mastoparan has two opposite effects on [Ca2+](i) in human astrocytoma cells and possibly has at least two sites of action.