Quantitative Changes in G Proteins Do Not Mediate Ethanol‐Induced Downregulation of Adenylyl Cyclase in Mouse Cerebral Cortex

Authors

• Boris Tabakoff, University of Colorado Anschutz Medical Campus
• James P. Whelan, University of Colorado Anschutz Medical Campus
• Larissa Ovchinnikova, University of Colorado Anschutz Medical Campus
• Patson Nhamburo, University of Colorado Anschutz Medical Campus
• Masami Yoshimura, University of Colorado Anschutz Medical Campus
• Paula L. Hoffman, University of Colorado Anschutz Medical Campus

Abstract

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 Gs (Gsα), G1α1–3Goα 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 G1α1, and Goα 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 EC50 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. Copyright © 1995, Wiley Blackwell. All rights reserved

Publication Title

Alcoholism Clinical and Experimental Research

Recommended Citation

Tabakoff, B., Whelan, J., Ovchinnikova, L., Nhamburo, P., Yoshimura, M., & Hoffman, P. (1995). Quantitative Changes in G Proteins Do Not Mediate Ethanol‐Induced Downregulation of Adenylyl Cyclase in Mouse Cerebral Cortex. Alcoholism Clinical and Experimental Research, 19 (1), 187-194. https://doi.org/10.1111/j.1530-0277.1995.tb01491.x