Ethanol and phosphatidylethanol reduce the binding of [3H]inositol 1,4,5-trisphosphate to rat cerebellar membranes.

In this study, we have analysed the effect of ethanol and phosphatidylethanol, a unique phospholipid formed only in the presence of ethanol, on the binding of [3H]inositol 1,4,5-trisphosphate to rat cerebellar membranes. Rats were intraperitoneally injected daily with 3 g of ethanol/kg body weight for different periods of time. Repeated administration of ethanol induced a reduction in the binding capacity (Bmax) without affecting the affinity constant (Kd). A significant 32% reduction was observed after 21 days of exposure (from control Bmax values of 25 +/- 3 pmol/mg and Kd values of 9 +/- 2 nM). In an in-vitro assay, phosphatidylethanol (500 microM) and phosphatidic acid (500 microM, but no other phospholipids tested, induced a reduction in Bmax (39% and 43%, respectively). The observed effect displayed by phosphatidylethanol was not due to its degradation to phosphatidic acid or other phospholipids. The results emphasize the importance of examining phosphatidylethanol (PEth) as a possible mediator of the effects of ethanol on cellular processes. However, the role of PEth in the observed effect of long-term ethanol exposure still needs further consideration.