NDLI: Mutant mice lacking the gamma isoform of protein kinase C show decreased behavioral actions of ethanol and altered function of gamma-aminobutyrate type A receptors.

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Mutant mice lacking the gamma isoform of protein kinase C show decreased behavioral actions of ethanol and altered function of gamma-aminobutyrate type A receptors.

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Mutant mice lacking the gamma isoform of protein kinase C show decreased behavioral actions of ethanol and altered function of gamma-aminobutyrate type A receptors.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Mcquilkin, S. J. Paylor, R. Abeliovich, A. Harris, R. A. Tonegawa, S. Wehner, J. M.
Description	Author Affiliation: Harris RA ( Denver Veterans Affairs Medical Center, CO, USA.);
Abstract	Calcium/phospholipid-dependent protein kinase (protein kinase C, PKC) has been suggested to play a role in the sensitivity of gamma-aminobutyrate type A (GABAA) receptors to ethanol. We tested a line of null mutant mice that lacks the gamma isoform of PKC (PKC gamma) to determine the role of this brain-specific isoenzyme in ethanol sensitivity. We found that the mutation reduced the amount of PKC gamma immunoreactivity in cerebellum to undetectable levels without altering the levels of the alpha, beta I, or beta II isoforms of PKC. The mutant mice display reduced sensitivity to the effects of ethanol on loss of righting reflex and hypothermia but show normal responses to flunitrazepam or pentobarbital. Likewise, GABAA receptor function of isolated brain membranes showed that the mutation abolished the action of ethanol but did not alter actions of flunitrazepam or pentobarbital. These studies show the unique interactions of ethanol with GABAA receptors and suggest protein kinase isoenzymes as possible determinants of genetic differences in response to ethanol.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	9
Volume Number	92
Language	English
Publisher	National Academy of Sciences
Publisher Date	1995-06-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Cerebellum Metabolism Cerebral Cortex Ethanol Pharmacology Isoenzymes Deficiency Protein Kinase C Receptors, GABA-A Physiology Animals Body Temperature Drug Effects Chlorides DNA Primers Blood Flunitrazepam Genetics Mice Mice, Mutant Strains Molecular Sequence Data Pentobarbital Polymerase Chain Reaction Posture Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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