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 microM, 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.