Ethanol alters the inhibitory effect of calcium ions on [3H]-inositol 1,4,5-trisphosphate binding

In this study we have analysed the effects of ethanol and divalent cations on the binding of [H-3]-inositol 1,4,5 trisphosphate to rat cerebellar membranes. Rats were injected intraperitoneally, daily, with 3 g of ethanol/kg of body weight for different periods of time. Repeated in vivo administration of ethanol caused a reduction of about 30% of binding in an in vitro assay carried out in the presence of 1 mM EDTA. With an IC50 of approximately 250 nM calcium ions produced a reduction In binding to cerebellar membranes isolated from control vats. The inhibitory effect was not observed in membranes taken from animals injected with alcohol for 21 days. Magnesium and manganese ions also lowered IP3 binding. The metabolic degradation of IP3 to IP3 was increased by magnesium and manganese but not by calcium and was similar in control and ethanol-treated rats. The results indicate that ethanol repeatedly administered to rats modifies the sensitivity of the IP3 receptor to calcium ion, but that it does not alter the metabolic fate of IP3 to IP2. This supports the idea that ethanol may have preferable targets within the cell.