Research article summary (published 20 Sep 2006):

Differential effects of systemic ethanol administration on protein kinase cepsilon, gamma, and beta isoform expression, membrane translocation, and target phosphorylation: reversal by chronic ethanol exposure.

Full Abstract

Systemic ethanol administration alters protein kinase C (PKC) activity in brain, but the effects of ethanol on the expression and translocation of specific isoforms are unknown. Rats were administered ethanol (2 g/kg i.p.) or saline and PKC levels were measured in the cytosolic and membrane fractions by Western blot analysis. PKCepsilon expression was increased in the cytosol and decreased in the membrane (P2) fraction of cerebral cortex at 10 min. At 60 min, expression of PKCepsilon in the P2 fraction was increased by 42.2 +/- 12%, but cytosolic levels were unchanged. In contrast, PKCgamma in the P2 fraction was decreased 32.7 +/- 7% at 60 min but not at 10 min post-ethanol administration. PKCgamma levels in the cytosol were reduced at 10 min post-ethanol administration and unchanged at 60 min. PKCbeta expression was increased 36 +/- 10 and 144 +/- 52% in the P2 fraction both at 10 and 60 min post-ethanol administration, whereas cytosolic levels were unchanged. Serine phosphorylation of GABA(A) receptor beta-chain was reduced, and phosphorylation of N-methyl-d-aspartate receptor NR1 subunit was increased 60 min following ethanol administration. There was no effect of acute ethanol administration on PKC isoform levels in the hippocampus. Ethanol challenge did not alter PKC isoform expression in the P2 fraction of cerebral cortex following chronic ethanol administration. These findings suggest that acute ethanol administration alters PKC synthesis and translocation in an isoform and brain region specific manner that leads to alterations in serine phosphorylation of receptors. Furthermore, chronic ethanol administration prevents ethanol-induced alterations in PKC expression in the P2 fraction, where PKC interacts with ethanol-responsive ion channels.

Author information

Author/s: Kumar, S (S); Lane, B M (BM); Morrow, A L (AL);

Affiliation: Department of Psychiatry, Bowles Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599-7178, USA.

Grants: AA015409 (Agency:NIAAA NIH HHS) ; AA11605 (Agency:NIAAA NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural

Journal: The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther), published in United States. (Language: eng)

Reference: 2006-Dec; vol 319 (issue 3) : pp 1366-75

Dates: Created 2006/11/19; Completed 2007/01/09; Revised 2007/11/15;

PMID: 16997974, status: MEDLINE (last retrieved date: 2/18/2009)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MeSH Headings (categories) shown below.

Animals Blotting, Western Central Nervous System Depressants - blood; pharmacology Cytosol - drug effects; enzymology; metabolism Drug Tolerance Ethanol - blood; pharmacology Food, Formulated Immunoprecipitation Isoenzymes - biosynthesis Male Phosphorylation

Phosphorylation Phosphoserine - metabolism Protein Kinase C - biosynthesis Protein Kinase C-epsilon - biosynthesis Protein Transport - drug effects Rats Rats, Sprague-Dawley Receptors, GABA-A - drug effects; metabolism Receptors, N-Methyl-D-Aspartate - drug effects Serine - metabolism Subcellular Fractions - drug effects; enzymology

Note: Bold headings indicate primary MeSH headings or qualifiers.

Associated Chemicals: Central Nervous System Depressants (0) ; Isoenzymes (0) ; NR1 NMDA receptor (0) ; Receptors, GABA-A (0) ; Receptors, N-Methyl-D-Aspartate (0) ; Phosphoserine (17885-08-4) ; Serine (56-45-1) ; Ethanol (64-17-5) ; protein kinase C beta (EC 2.7.1.-) ; protein kinase C gamma (EC 2.7.1.-) ; Protein Kinase C-epsilon (EC 2.7.1.37) ; Protein Kinase C (EC 2.7.11.13)

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