J. Lepetitthevenin et al., REVERSIBLE INHIBITION BY ETHANOL OF MG2(-DEPENDENT PHOSPHATIDATE PHOSPHOHYDROLASE - AN IN-VITRO STUDY IN THE RAT RETICULOCYTE()), Biochimica et biophysica acta, L. Lipids and lipid metabolism, 1257(2), 1995, pp. 111-117
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.