Changes of G-protein levels in platelet membranes from alcoholics during short-term and long-term abstinence.
The levels of G alpha i2-protein and the G beta gamma-heterodimer were measured in platelet membranes of non-alcoholics, non-alcoholics after an ethanol load (1 g/kg body weight) and of alcoholics under various conditions. The findings were correlated with the activation of the adenylyl cyclase (AC) by various agents. The activation of AC was facilitated by acute ingestion of ethanol. This could not be explained by changes of the G-proteins determined because the levels of the G alpha i2-protein increased, whereas those of the G beta gamma-proteins remained in the control range. The alcoholics were divided into two groups on the day of admission: those with ethanol still present in the blood (intoxicated alcoholics) and those acutely withdrawn within the last 48 h (ethanol absent from the blood). The intoxicated alcoholics had elevated G alpha i2-protein levels in contrast to the acutely withdrawn patients, who did not. This observation suggests rapid changes of the G-protein levels. By analysing the inhibitory efficacy of the G-proteins on AC, it was found that the concentration of the G beta gamma-heterodimer, but not that of the G alpha i2-proteins, correlated with the inhibitory efficacy. The basal activity of the AC was reduced as well as the activation by some compounds. Eight days later (short-term withdrawal) both the levels of G alpha i2 and G beta gamma were elevated. Again, the inhibitory efficacy of the G-proteins correlated with the G beta gamma-heterodimer levels but not with those of the G alpha i2-protein. Furthermore, the changes of the G beta gamma-protein levels between the first and the eighth day correlated with the changes of the inhibiting efficacy. Only a trend was observed with respect to a lowered basal activity if compared with the intoxicated non-alcoholics. The activation of AC by guanylylimidyldiphosphate [Gpp(NH)p] and Gpp(NH)p + ethanol (200 mM in vitro) was still reduced. Observations after 3 and 6 months of abstinence demonstrated elevated G alpha i2- and G beta gamma-protein levels. This suggests residual marker properties of the G-proteins whereby the activity of AC was normal. Only the reduced stimulation by Gpp(NH)p + ethanol in vitro (200 mM), compared with the respective stimulation of AC of intoxicated non-alcoholics, suggested some residual disturbances of the signal transduction during long-term abstinence.
Department of Neuropsychopharmacology, Free University of Berlin, Germany.
B
B
Lichtenberg-Kraag
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T
May
L G
LG
Schmidt
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H
Rommelspacher
D000262:Adenylyl Cyclases / Q000378:metabolism; D000428:Alcohol Drinking; D000437:Alcoholism / Q000097:blood*; D001792:Blood Platelets / Q000187:drug effects*; D002462:Cell Membrane / Q000187:drug effects; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006165:Guanylyl Imidodiphosphate / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D013695:Temperance
D006165:Guanylyl Imidodiphosphate; D000431:Ethanol; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases