Phosphatidylethanol is formed by
phospholipase D in animal cells exposed to
ethanol. Previous reports have demonstrated that the degradation of
phosphatidylethanol is slow, indicating that this
lipid may be present in the cells after
ethanol itself has disappeared. Accumulation of an abnormal alcohol metabolite may influence cellular functions. In the present study, cultivation of NG108-15
neuroblastoma x
glioma hybrid cells in the presence of
ethanol resulted in an accumulation of
phosphatidylethanol and a simultaneous increase in basal
inositol 1,4,5-trisphosphate levels. The direct effects of
phosphatidylethanol on the
phosphoinositide signal transduction system were examined through incorporation of exogenous
phosphatidylethanol into membranes of
ethanol-naive cells. An incorporation amounting to 2.8% of cellular
phospholipids was achieved after a 5-h incubation with 30 microM
phosphatidylethanol.
Phosphatidylethanol was found to cause a time- and dose-dependent increase in the basal levels of
inositol 1,4,5-trisphosphate. The effects on
inositol 1,4,5-trisphosphate levels of exogenously added
phosphatidylethanol and
ethanol exposure for 2 days were not additive. No effect on
bradykinin-stimulated
inositol 1,4,5-trisphosphate production could be detected. However, the increase in basal
inositol 1,4,5-trisphosphate levels indicates that
phosphatidylethanol affects
inositol 1,4,5-trisphosphate turnover and emphasizes the importance of considering
phosphatidylethanol as a possible mediator of
ethanol-induced effects on cellular processes.