Genetically determined alcohol preference and cyclic AMP binding proteins in mouse brain.
Free-choice consumption of alcohol by mice with differing phenotypic alcohol preferences caused uniformly large decreases in brain cyclic AMP-dependent protein kinase activity toward an exogenous substrate (histone 2b) but the effect of alcohol on brain cyclic AMP binding activity was strain-specific. Furthermore, particulate kinase phosphorylating activity toward an endogenous protein (kinase regulatory subunit, RII) was altered by alcohol consumption in a strain-specific manner. The changes in cyclic AMP binding and phosphorylating activity appeared to result from phenotypic differences in the brain's response to alcohol. Thus, low preference animals were sensitive to alcohol and showed a large decrease in cyclic AMP binding and an increase in phosphorylation of regulatory subunit in response to alcohol. In contrast, high preference strain had only a small decrease in cyclic AMP binding and a decrease in phosphorylation, even though these animals consumed a significantly larger dose of alcohol. These data suggest that changes in cyclic AMP binding and/or phosphorylation of kinase regulatory subunit may be phenotypic markers of alcohol preference in inbred mice.
Beeker
K R
KR
Department of Biochemistry, East Carolina University, School of Medicine, Greenville, North Carolina 27834.
Lee
R C
RC
Phung
H M
HM
Smith
C P
CP
Pennington
S N
SN
D000437:Alcoholism / Q000235:genetics*; D000818:Animals; D001921:Brain / Q000201:enzymology*; D002352:Carrier Proteins / Q000235:genetics*; D000242:Cyclic AMP / Q000235:genetics; D002373:Cyclic AMP Receptor Protein; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010641:Phenotype; D011458:Prostaglandins E / Q000235:genetics; D011494:Protein Kinases / Q000235:genetics*
D002352:Carrier Proteins; D002373:Cyclic AMP Receptor Protein; D011458:Prostaglandins E; D000242:Cyclic AMP; D011494:Protein Kinases