Effects of acute ethanol administration on polyphosphoinositide turnover and levels of inositol 1,4,5-trisphosphate in mouse cerebrum and cerebellum.
Although ethanol is known for its central depressant action, its effect on the polyphosphoinositide (poly-PI) signal transduction activity in brain has not been examined in detail. In this study, C57Bl/6J mice were injected intracerebrally with [3H]inositol, and poly-PI turnover in brain was assessed by determining the levels of labeled inositol monophosphates (IP1) accumulated after intraperitoneal injection of LiCl (6 meq/kg body weight) 4 hr before killing. Using this experimental protocol, acute ethanol administration (by gavage) resulted in time- and dose-dependent decreases in the levels of labeled IP1 in both cerebrum and cerebellum as compared with controls. The ethanol-induced decrease in labeled IP1 correlated well with the decrease in levels of inositol 1,4,5-triphosphate (as measured by the radioreceptor assay) and the increase in blood ethanol concentration. Despite a 4-fold higher accumulation of labeled IP1 in the cerebrum compared with the cerebellum, there were no major differences in the steady-state levels of inositol 1,4,5-triphosphate (based on tissue weight) in either brain region. Intraperitoneal injection of atropine (50 mg/kg) (a muscarinic cholinergic receptor antagonist) to the lithium-treated mice resulted in a 34% decrease in labeled IP1 as compared with controls. This result suggests that a substantial proportion of the signals transduced were due to activation of the muscarinic cholinergic receptor. Administration of ethanol (5 g/kg) to the atropine-treated mice resulted in a further decrease in labeled IP1 and longer sleep time as compared with those given ethanol alone.(ABSTRACT TRUNCATED AT 250 WORDS)
Biochemistry Department, University of Missouri, Columbia.
T A
TA
Lin
M
M
Navidi
W
W
James
T N
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Lin
G Y
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Sun
D000437:Alcoholism / Q000473:pathology*; D000818:Animals; D001921:Brain / Q000473:pathology*; D002531:Cerebellum / Q000187:drug effects* / Q000473:pathology; D002540:Cerebral Cortex / Q000187:drug effects* / Q000473:pathology; D000431:Ethanol / Q000493:pharmacokinetics; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010716:Phosphatidylinositols / Q000378:metabolism*
D010716:Phosphatidylinositols; D000431:Ethanol; D015544:Inositol 1,4,5-Trisphosphate