Ethanol and inositol 1,4,5-trisphosphate mobilize calcium from rat brain microsomes

The effects of ethanol on ATP-dependent Ca²⁺ uptake and inositol 1,4,5 trisphosphate (Ins-P₃)-induced Ca²⁺ release were assessed in rat cerebellar and cortical microsomes. Ins-P₃, 0.2-10 μM, released 7-14% of ATP loaded microsomal Ca²⁺ stores after a 15-sec exposure. Ethanol, 250-750 mM, added after ATP-dependent loading, significantly released microsomal Ca²⁺ stores, and the amount released was additive to that seen with Ins-P₃ alone. The presence of ethanol, 250-750 mM, during the ATP-dependent loading period, resulted in decreased Ca²⁺ uptake that correlated with decreases in Ins-P₃-induced Ca²⁺ release. Chronic ethanol treatment failed to produce any alterations in ethanol's ability to promote Ca²⁺ release or to inhibit ATP-dependent Ca²⁺ uptake. Furthermore, Ins.-P₃-induced Ca²⁺ release was not altered by chronic ethanol treatment. These results suggest that Ins-P₃ sensitive Ca²⁺ stores are resistant to pharmacologically relevant concentrations of ethanol, and do not appear to be involved in the chronic cellular effects of ethanol.