JPET Assistant Professor of Medicine (Clinician-Educator)

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Findlay, G. S.
Right arrow Articles by Blednov, Y. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Findlay, G. S.
Right arrow Articles by Blednov, Y. A.
Right arrowPubmed/NCBI databases
*Compound via MeSH
*Substance via MeSH
Hazardous Substances DB
*ETHANOL
*GLYCINE
*STRYCHNINE

Vol. 300, Issue 2, 526-534, February 2002

Transgenic Expression of a Mutant Glycine Receptor Decreases Alcohol Sensitivity of Mice

G. S. Findlay, M. J. Wick1, M. P. Mascia2, D. Wallace, G. W. Miller, R. A. Harris and Y. A. Blednov

Waggoner Center for Alcohol and Addiction Research, Section of Neurobiology, University of Texas at Austin, Austin, Texas

Glycine receptors (GlyRs) are pentameric ligand-gated ion channels that inhibit neurotransmission in the adult brainstem and spinal cord. GlyR function is potentiated by ethanol in vitro, and a mutant GlyR subunit alpha 1(S267Q) is insensitive to the potentiating effects of ethanol. To test the importance of GlyR for the actions of ethanol in vivo, we constructed transgenic mice with this mutation. Under the control of synapsin I regulatory sequences, transgenic expression of S267Q mutant GlyR alpha 1 subunits in the nervous system was demonstrated using [3H]strychnine binding and immunoblotting. These mice showed decreased sensitivity to ethanol in three behavioral tests: ethanol inhibition of strychnine seizures, motor incoordination (rotarod), and loss of righting reflex. There was no change in ethanol sensitivity in tests of acute functional tolerance or body temperature, and there was no change in ethanol metabolism. Transgene effects were pharmacologically specific for ethanol, compared with pentobarbital, flurazepam, and ketamine. These results support the idea that glycine receptors contribute to some behavioral actions of ethanol and that ethanol sensitivity can be changed in vivo by transgenic expression of a single receptor subunit.

1 Current address: Department of Medicine, Division of Renal Diseases and Hypertension, University of Colorado Health Sciences Center, Denver, CO 80282.

2 Current address: Consiglio Nazionale delle Ricerche, Dip. Di Biologia Sperimentale (Sezione di Neuroscienze), Cittadella Universitaria, SS 554 (Km 4.500), 09042 Monserrato, Cagliari, Italy.

0022-3565/02/3002-0526$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 2002 by The American Society for Pharmacology and Experimental Therapeutics


This article has been cited by other articles:


Home page
 J. Pharmacol. Exp. Ther.Home page
B. T. Welsh, B. E. Goldstein, and S. J. Mihic
Single-Channel Analysis of Ethanol Enhancement of Glycine Receptor Function
J. Pharmacol. Exp. Ther., July 1, 2009; 330(1): 198 - 205.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. T. Roberts, R. Phelan, B. S. Erlichman, R. N. Pillai, L. Ma, G. F. Lopreato, and S. J. Mihic
Occupancy of a Single Anesthetic Binding Pocket Is Sufficient to Enhance Glycine Receptor Function
J. Biol. Chem., February 10, 2006; 281(6): 3305 - 3311.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
T. J. Shafer, P. J. Bushnell, V. A. Benignus, and J. J. Woodward
Perturbation of Voltage-Sensitive Ca2+ Channel Function by Volatile Organic Solvents
J. Pharmacol. Exp. Ther., December 1, 2005; 315(3): 1109 - 1118.
[Abstract] [Full Text] [PDF]

Home page
 Sci SignalHome page
D. Ron and R. Jurd
The "Ups and Downs" of Signaling Cascades in Addiction
Sci. Signal., November 8, 2005; 2005(309): re14 - re14.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
P. M. Newton, C. J. Orr, M. J. Wallace, C. Kim, H.-S. Shin, and R. O. Messing
Deletion of N-Type Calcium Channels Alters Ethanol Reward and Reduces Ethanol Consumption in Mice
J. Neurosci., November 3, 2004; 24(44): 9862 - 9869.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
J. W. Lynch
Molecular Structure and Function of the Glycine Receptor Chloride Channel
Physiol Rev, October 1, 2004; 84(4): 1051 - 1095.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
I. A. Lobo, M. P. Mascia, J. R. Trudell, and R. A. Harris
Channel Gating of the Glycine Receptor Changes Accessibility to Residues Implicated in Receptor Potentiation by Alcohols and Anesthetics
J. Biol. Chem., August 6, 2004; 279(32): 33919 - 33927.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
G. S. Findlay, R. Phelan, M. T. Roberts, G. E. Homanics, S. E. Bergeson, G. F. Lopreato, S. J. Mihic, Y. A. Blednov, and R. A. Harris
Glycine Receptor Knock-In Mice and Hyperekplexia-Like Phenotypes: Comparisons with the Null Mutant
J. Neurosci., September 3, 2003; 23(22): 8051 - 8059.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2002 by the American Society for Pharmacology and Experimental Therapeutics.