Differential effects of norepinephrine on phosphatidylinositol 4,5-bisphosphate stimulated hydrolysis in brains of mice genetically selected for differences in ethanol sensitivity.
The effects of norepinephrine on phosphoinositide turnover were evaluated in five brain regions of the long sleep (LS) and short sleep (SS) mice. These mice were selectively bred for differences in central nervous system sensitivity to ethanol with the LS exhibiting much greater sensitivity to a hypnotic dose of ethanol than the SS, as determined by the ability of the mice to regain their righting reflex. Norepinephrine (10(-3) M, 10(-4) M, and 10(-5) M) significantly increased phosphoinositide turnover in the hippocampus, hypothalamus, locus ceruleus, cerebellum, and cortex within each line of mice. Basal and norepinephrine-stimulated phosphoinositide turnover were significantly higher in the SS mice as compared with the LS mice in the cerebellum and cortex but not the other brain regions. Incorporation of 3H-inositol into 3H-phosphatidylinositols was not different between SS and LS mice in the cerebellum and cortex. The greater norepinephrine-stimulated phosphoinositide turnover in the cerebellum and cortex of the SS versus the LS mice may contribute to the CNS sensitivity to ethanol in these two lines of mice. However, ethanol (500 mM) had no effect on basal or norepinephrine-stimulated phosphoinositide turnover in any of the five brain areas examined in the LS and SS mice.
Weiner
E A
EA
Department of Pharmacology (C236), University of Colorado Health Sciences Center, Denver 80262.
French
T A
TA
Baker
R C
RC
Masserano
J M
JM
D000818:Animals; D001143:Arousal / Q000187:drug effects* / Q000235:genetics; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004075:Diglycerides / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D009638:Norepinephrine / Q000494:pharmacology*; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols / Q000378:metabolism*; D015290:Second Messenger Systems / Q000187:drug effects / Q000235:genetics; D012641:Selection, Genetic; D012894:Sleep Stages / Q000187:drug effects* / Q000235:genetics
C011439:1,2-diacylglycerol; D004075:Diglycerides; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols; D000431:Ethanol; D015544:Inositol 1,4,5-Trisphosphate; D009638:Norepinephrine