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Sci. Signal., 15 July 2008
Vol. 1, Issue 28, p. re7
[DOI: 10.1126/scisignal.128re7]


Ethanol’s Molecular Targets

R. Adron Harris1*, James R. Trudell2, and S. John Mihic1

1Section of Neurobiology and Waggoner Center for Alcohol and Addiction Research, Institutes for Neuroscience and Cell & Molecular Biology, University of Texas, Austin, TX 78712, USA.
2Department of Anesthesia, Stanford University School of Medicine, Stanford, CA 94305, USA.

Gloss: For much of the 20th century, it was widely believed that ethanol exerts its effects on neuronal function in a nonspecific manner—perhaps through the disordering of membrane lipids. However, over the past two decades, evidence has mounted that ethanol instead produces its effects by altering the functioning of specific proteins through its interaction with a select few amino acids in those proteins. In this Review with 2 figures and 60 citations, we focus on proteins for which evidence for specific alcohol binding sites has been obtained, and we briefly describe and compare these ethanol receptors.

*Corresponding author. E-mail, harris{at}

Citation: R. A. Harris, J. R. Trudell, S. J. Mihic, Ethanol’s Molecular Targets. Sci. Signal. 1, re7 (2008).

Seeking Structural Specificity: Direct Modulation of Pentameric Ligand-Gated Ion Channels by Alcohols and General Anesthetics.
R. J. Howard, J. R. Trudell, and R. A. Harris (2014)
Pharmacol. Rev. 66, 396-412
   Abstract »    Full Text »    PDF »
Molecular mechanism underlying ethanol activation of G-protein-gated inwardly rectifying potassium channels.
K. Bodhinathan and P. A. Slesinger (2013)
PNAS 110, 18309-18314
   Abstract »    Full Text »    PDF »
Distinct molecular targets including SLO-1 and gap junctions are engaged across a continuum of ethanol concentrations in Caenorhabditis elegans.
J. Dillon, I. Andrianakis, R. Mould, B. Ient, W. Liu, C. James, V. O'Connor, and L. Holden-Dye (2013)
FASEB J 27, 4266-4278
   Abstract »    Full Text »    PDF »
A Common Molecular Basis for Exogenous and Endogenous Cannabinoid Potentiation of Glycine Receptors.
W. Xiong, X. Wu, D. M. Lovinger, and L. Zhang (2012)
J. Neurosci. 32, 5200-5208
   Abstract »    Full Text »    PDF »
The Basic Property of Lys385 Is Important for Potentiation of the Human {alpha}1 Glycine Receptor by Ethanol.
P. A. Castro, M. Figueroa, G. E. Yevenes, L. S. San Martin, and L. G. Aguayo (2012)
J. Pharmacol. Exp. Ther. 340, 339-349
   Abstract »    Full Text »    PDF »
The TM2 6' Position of GABAA Receptors Mediates Alcohol Inhibition.
W. D. Johnson II, R. J. Howard, J. R. Trudell, and R. A. Harris (2012)
J. Pharmacol. Exp. Ther. 340, 445-456
   Abstract »    Full Text »    PDF »
Structural basis for alcohol modulation of a pentameric ligand-gated ion channel.
R. J. Howard, S. Murail, K. E. Ondricek, P.-J. Corringer, E. Lindahl, J. R. Trudell, and R. A. Harris (2011)
PNAS 108, 12149-12154
   Abstract »    Full Text »    PDF »
Two Alcohol Binding Residues Interact across a Domain Interface of the L1 Neural Cell Adhesion Molecule and Regulate Cell Adhesion.
X. Dou, C. E. Menkari, S. Shanmugasundararaj, K. W. Miller, and M. E. Charness (2011)
J. Biol. Chem. 286, 16131-16139
   Abstract »    Full Text »    PDF »
Inhibition of Recombinant L-Type Voltage-Gated Calcium Channels by Positive Allosteric Modulators of GABAA Receptors.
D. E. Earl and E. I. Tietz (2011)
J. Pharmacol. Exp. Ther. 337, 301-311
   Abstract »    Full Text »    PDF »
Extrasynaptic {delta}-containing GABAA receptors in the nucleus accumbens dorsomedial shell contribute to alcohol intake.
H. Nie, M. Rewal, T. M. Gill, D. Ron, and P. H. Janak (2011)
PNAS 108, 4459-4464
   Abstract »    Full Text »    PDF »
Binge alcohol drinking is associated with GABAA {alpha}2-regulated Toll-like receptor 4 (TLR4) expression in the central amygdala.
J. Liu, A. R. Yang, T. Kelly, A. Puche, C. Esoga, H. L. June Jr., A. Elnabawi, I. Merchenthaler, W. Sieghart, H. L. June Sr., et al. (2011)
PNAS 108, 4465-4470
   Abstract »    Full Text »    PDF »
Loss of Ethanol Conditioned Taste Aversion and Motor Stimulation in Knockin Mice with Ethanol-Insensitive {alpha}2-Containing GABAA Receptors.
Y. A. Blednov, C. M. Borghese, M. L. McCracken, J. M. Benavidez, C. R. Geil, E. Osterndorff-Kahanek, D. F. Werner, S. Iyer, A. Swihart, N. L. Harrison, et al. (2011)
J. Pharmacol. Exp. Ther. 336, 145-154
   Abstract »    Full Text »    PDF »
Ethanol Upregulates Glucocorticoid-Induced Leucine Zipper Expression and Modulates Cellular Inflammatory Responses in Lung Epithelial Cells.
M. Gomez, S. V. Raju, A. Viswanathan, R. G. Painter, R. Bonvillain, P. Byrne, D. H. Nguyen, G. J. Bagby, J. K. Kolls, S. Nelson, et al. (2010)
J. Immunol. 184, 5715-5722
   Abstract »    Full Text »    PDF »
Mice Selectively Bred for High- or Low-Alcohol-Induced Locomotion Exhibit Differences in Dopamine Neuron Function.
M. J. Beckstead and T. J. Phillips (2009)
J. Pharmacol. Exp. Ther. 329, 342-349
   Abstract »    Full Text »    PDF »
Acute Alcohol Action and Desensitization of Ligand-Gated Ion Channels.
A. M. Dopico and D. M. Lovinger (2009)
Pharmacol. Rev. 61, 98-114
   Abstract »    Full Text »    PDF »
Science Signaling Podcast: 15 July 2008.
J. F. Foley and A. M. VanHook (2008)
Science Signaling 1, pc6
   Abstract »    Full Text »

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