Reversible inhibition by ethanol of Mg(2+)-dependent phosphatidate phosphohydrolase: an in vitro study in the rat reticulocyte.
By using a tracer method, we demonstrate that short-term in vitro exposure of intact rat reticulocytes to ethanol elicits a biphasic response of cell-bound Mg(2+)-dependent phosphatidate phosphohydrolase (PAP). An initial concentration-dependent (200-750 mM) activity decrease is rapidly (< 10 min) followed by reversal of the inhibition in the presence of ethanol, suggesting the development of a cell resistance to the inhibitory agent. Addition to the cell suspension of propranolol (100 microM), a known PAP inhibitor, does elicit PAP inhibition but unlike ethanol, inhibition is not followed by a return with time to control value. Ethanol-induced inhibition of cell-bound PAP was also demonstrated in cell-free extracts, where the Mg(2+)-dependent activity was decreased both in the particulate and soluble fractions. In the intact cells, the transient PAP inhibition occurs in concomitance with an overall increase in total glycerolipid biosynthesis, which is constant over 60-min incubation. We suggest that the biphasic mode of response to ethanol of Mg(2+)-dependent PAP activity may play a role in the mechanism of membrane adaptation to ethanol, and thereby to the pathogenesis of alcoholism.
Le Petit-Thevenin
J
J
Unité 260, l'Institut National de la Santé et de la Recherche Médicale, Faculté de Médecine Timone, Marseille, France.
Nobili
O
O
Vérine
A
A
Somma-Delpéro
C
C
Boyer
J
J
D000222:Adaptation, Physiological; D000818:Animals; D002250:Carbon Radioisotopes; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D004789:Enzyme Activation / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D005989:Glycerides / Q000096:biosynthesis; D066298:In Vitro Techniques; D008274:Magnesium / Q000378:metabolism*; D010711:Phosphatidate Phosphatase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012156:Reticulocytes / Q000201:enzymology*
D002250:Carbon Radioisotopes; D005989:Glycerides; D000431:Ethanol; D010711:Phosphatidate Phosphatase; D008274:Magnesium