REVERSIBLE INHIBITION BY ETHANOL OF MG2(-DEPENDENT PHOSPHATIDATE PHOSPHOHYDROLASE - AN IN-VITRO STUDY IN THE RAT RETICULOCYTE())

By using a tracer method, we demonstrate that short-term in vitro expo sure of intact rat reticulocytes to ethanol elicits a biphasic respons e of cell-bound Mg2+-dependent phosphatidate phosphohydrolase (PAP). A n initial concentration-dependent (200-750 mM) activity decrease is ra pidly (< 10 min) followed by reversal of the inhibition in the presenc e of ethanol, suggesting the development of a cell resistance to the i nhibitory agent. Addition to the cell suspension of propranolol (100 m u M), a known PAP inhibitor, does elicit PAP inhibition but unlike eth anol, inhibition is not followed by a return with time to control valu e. Ethanol-induced inhibition of cell-bound PAP was also demonstrated in cell-free extracts, where the Mg2+-dependent activity was decreased both in the particulate and soluble fractions. In the intact cells, t he transient PAP inhibition occurs in concomitance with an overall inc rease in total glycerolipid biosynthesis, which is constant over 60-mi n incubation. We suggest that the biphasic mode of response to ethanol of Mg2+-dependent PAP activity may play a role in the mechanism of me mbrane adaptation to ethanol, and thereby to the pathogenesis of alcoh olism.