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Quantitative Changes in G Proteins Do Not Mediate Ethanol‐Induced Downregulation of Adenylyl Cyclase in Mouse Cerebral Cortex
Author(s) -
Tabakoff Boris,
Whelan James P.,
Ovchinnikova Larissa,
Nhamburo Patson,
Yoshimura Masami,
Hoffman Paula L.
Publication year - 1995
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.1995.tb01491.x
Subject(s) - adenylyl cyclase , forskolin , g protein , adcy9 , cerebral cortex , medicine , endocrinology , adcy10 , chemistry , gs alpha subunit , biology , biochemistry , receptor , stimulation
Our prior work, and the work of others, demonstrated that chronic administration of ethanol to cells in culture or to mice resulted in decreased responsiveness of adenylyl cyclase (EC4.6.1.1) to a number of stimulatory agents. In this study, we substantiated the ethanol‐induced changes in cerebral cortical adenylyl cyclase activity in alcohol‐tolerant and alcohol‐dependent mice, and we examined whether chronic ethanol treatment of mice altered the quantity of heterotrimeric guanine nucleotide‐binding regulatory proteins (G proteins) in cerebral cortex and other mouse brain areas. Amounts of various G protein subunits‐including the α subunits of G s (G s α), G 1 α 1–3 G o α and β subunits‐were examined by Western blot analysis. There was no change in quantity of these G protein subunits in cerebral cortex, hippocampus, or cerebellum of ethanol‐fed mice, compared with controls. In striatum of ethanol‐fed mice, small increases in G 1 α 1 , and G o α were observed, but these changes could not explain the ethanol‐induced desensitization of adenylyl cyclase in brain areas such as the cerebral cortex. Forskolin activation of cerebral cortical adenylyl cyclase activity showed two components of activation, with high and low “affinity” for forskolin. Ethanol treatment caused a decrease in the efficacy of forskolin for both components, whereas the EC 50 of forskolin for each component did not change. Adenylyl cyclase activity measured in the presence of manganese was also diminished in cortical membranes of ethanol‐treated mice. Our results indicate that chronic ethanol treatment does not cause quantitative changes in G proteins which correlate with ethanol‐induced changes in cortical adenylyl cyclase activity. The ethanol‐induced reduction in adenylyl cyclase activity could be observed using agents (forskolin and manganese) that directly activate the catalytic unit of this enzyme. Thus, our results suggest that chronic ethanol treatment may alter the activity of the catalytic unit of adenylyl cyclase.