Blood ethanol levels and adenylyl cyclase activity in lymphocytes of alcoholic patients

Abstract

Background: The adenylyl cyclase (AC) signal transduction pathway is a target of acute and chronic ethanol actions. This study examined whether AC activity in lymphocyte membranes of male alcoholic patients correlated with blood concentrations of ethanol. Methods: Patients ( n = 13; mean age: 40 ± 8 years) were studied on the day of admission (day 0) and 2 days later under detoxification. Moreover, 13 age-matched male healthy controls (mean age 40 ± 9 years) were included. Lymphocyte membranes were prepared by differential centrifugation whereby blood ethanol was washed out. As a measure of AC activity the formation of cyclic adenosine monophosphate (cAMP) from adenosine triphosphate was determined without (basal activity) and with stimulation of the second messenger system by the guanosine triphosphate (GTP) analogue GTPγS (20 μmol/L) via the G-protein or by forskolin (100 μmol/L) acting directly on the AC enzyme. Results: On day 0, when ethanol blood concentrations were 38–100 mmol/L, we found a significant negative correlation between ethanol blood levels and stimulated AC activities. On day 2, the negative correlation with blood ethanol levels of day 0 had disappeared. Conclusions: The consumption of ethanol affects the AC system in lymphocytes of alcohol-dependent patients by a persistent effect on the cAMP forming enzyme.