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[Changes in platelet adenylyl cyclase system in alcoholics]
Y Katamura1, T Saito, N Takahata
1Department of Neuropsychiatry, Sapporo Medical University School of Medicine, Japan.
Nihon Arukoru Yakubutsu Igakkai Zasshi = Japanese Journal of Alcohol Studies & Drug Dependence
|April 1, 1996
Summary
Platelet G protein alterations, specifically reduced adenylyl cyclase activity and GTP binding, were found in alcoholics with a family history of alcoholism. These changes suggest platelet G protein may serve as a trait marker for alcoholism.
Area of Science:
- Biochemistry
- Genetics
- Pharmacology
Background:
- Alcoholism is a complex disorder with potential genetic predispositions.
- G protein signaling pathways are implicated in various cellular functions and may be affected by chronic alcohol consumption.
- Identifying biological markers for alcoholism can aid in understanding its etiology and developing targeted interventions.
Purpose of the Study:
- To investigate platelet Guanine nucleotide-binding protein (G protein) characteristics in alcohol-dependent individuals.
- To determine if platelet G protein alterations serve as a trait marker for alcoholism, particularly in individuals with a family history.
- To assess the impact of family history on G protein function and ethanol sensitivity in alcoholics.
Main Methods:
- Compared platelet G protein activity, ethanol sensitivity, and G protein subunit levels in three groups: family history positive (FHP) alcoholics, family history negative (FHN) alcoholics, and controls.
- Assessed guanine nucleotide-stimulated adenylyl cyclase (AC) activity.
- Measured ethanol enhancement of photoaffinity GTP binding to Gs alpha and Gi alpha.
- Quantified Gs alpha and GsH alpha levels using immunoblotting.
Main Results:
- Family history positive (FHP) alcoholics exhibited lowered platelet adenylyl cyclase (AC) activity and reduced AC sensitivity to ethanol.
- FHP alcoholics showed a significant reduction in ethanol enhancement of GTP binding to Gs alpha and Gi alpha in platelet membranes.
- Quantitative reductions in Gs alpha and GsH alpha levels were observed in platelet membranes from FHP alcoholics compared to controls and FHN alcoholics.
Conclusions:
- Platelet G protein characteristics, including adenylyl cyclase activity and GTP binding, are altered in alcoholics with a family history of the disorder.
- These specific alterations in platelet G protein function and levels may serve as a biological trait marker for alcoholism.
- The findings suggest a potential genetic component influencing G protein pathways in the susceptibility to alcoholism.