0000000000262908

AUTHOR

Thorsten Pauly

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 triphospha…

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Adenylyl cyclase activity is increased in younger, but decreased in older, alcoholic patients after detoxification.

Acute and chronic administration of ethanol leads to alterations of the adenylyl cyclase (AC) signal transduction pathway. This study examined whether the formation of cAMP by AC in lymphocytes correlates with age in alcoholic patients and in healthy controls. Blood was drawn for preparation of lymphocyte membranes and for determination of basal, GTPgammaS-stimulated, and forskolin-stimulated AC activity from 68 actively drinking alcoholic patients (age, mean +/- SD: 45 +/- 10; range: 26-69 years) after ethanol detoxification. The patients' AC activity correlated negatively with age. In contrast, no effect of age was observed in the healthy controls (age, mean +/- SD: 42 +/- 11; range: 24-6…

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Neuronal Cell Nuclear Factor. A Nuclear Receptor Possibly Involved in the Control of Neurogenesis and Neuronal Differentiation

We have cloned from a cDNA library of neuronal derivatives of retinoic-acid-induced embryonic carcinoma cells a nuclear receptor that may be involved in the control of late neurogenesis and early neuronal differentiation. The receptor which is practically identical in sequence with germ cell nuclear factor, has been designated neuronal cell nuclear factor (NCNF). NCNF is exclusively expressed in the neuronal derivatives of PCC7-Mz1 cells, with the expression beginning within hours of exposure to retinoic acid. In the developing mouse brain, NCNF is expressed in the marginal zones of the neuroepithelium which are known to contain young postmitotic neurons. NCNF binds to the DRO sequence ther…

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Activity of the adenylyl cyclase in lymphocytes of male alcoholic patients is state dependent.

A decreased basal and/or stimulated activity of the G-protein/adenylyl cyclase (AC) system in peripheral blood cells has been proposed to represent a trait marker for alcoholism. However, AC activity may underlie state-dependent changes, which may impair a proper interpretation of AC activity measurements. Our study examined systematically the AC activity in peripheral lymphocytes of 73 male alcohol-dependent patients (according to DSM-IV criteria) at three different time points of measurement during the clinical course of detoxification (day 0 = at admission, while still ethanol-affected; day 2 = at the presumed peak of withdrawal symptoms; day E = after detoxification). Basal and stimulat…

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