Increase in Ca²⁺ permeability of intracellular Ca²⁺ store membrane of saponin-treated Guinea pig peritoneal macrophages by inositol 1,4,5-trisphosphate

Inositol 1,4,5-trisphosphate (InsP₃) releases Ca²⁺ from the non-mitochondrial Ca²⁺ store site of various types of cells. To study the mechanisms of the Ca²⁺ release from the store site, the effect of InsP₃ on the passive Ca²⁺ release and influx, and the active Ca²⁺ uptake in the presence of oxalate, was examined using saponintreated Guinea pig peritoneal macrophages. InsP₃ stimulated the passive Ca²⁺ release and influx. Although InsP₃ slightly inhibited the active Ca²⁺ uptake in the presence of oxalate, it seems unlikely that the Ca²⁺ release by this agent is caused by the inhibition of the Ca²⁺ uptake, because the addition of apyrase or hexokinase (which removes ATP within 30 s, so that no more Ca²⁺ can be accumulated) or vanadate (which inhibits the Ca²⁺ uptake) resulted in very slow release of Ca²⁺. These results suggest that the Ca²⁺ permeability of the Ca²⁺ store membrane is increased by InsP₃. InsP₃ did not cause an increase in the Ca²⁺ permeability of phospholipid vesicles (liposomes), indicating that this agent may bring about Ca²⁺ release by a specific effect on the physiologically relevant Ca²⁺ channels or carriers in the non-mitochondrial Ca²⁺ store site. The passive Ca²⁺ release by InsP₃ was enhanced by ATP and an unhydrolyzable ATP analogue, 5'-adenylyimidodiphosphate, but not by ADP or AMP. The passive Ca²⁺ release by InsP₃ was observed even at 0°C.