Effects of Acute Ethanol Administration on Polyphosphoinositide Turnover and Levels of Inositol 1,4,5‐Trisphosphate in Mouse Cerebrum and Cerebellum

Tai‐An ‐A Lin, Meena Navidi, William James, Teng‐Nan ‐N Lin, Grace Y. Sun

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10 Scopus citations

Abstract

Although ethanol is known for its central depressant action, its effect on the polyphosphoinositide (poly‐Pl) signal transduction activity in brain has not been examined in detail. In this study, C57BI/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. Taken together, these results indicate a relationship between the acute effect of ethanol and the poly‐PI signaling activity in brain and modulation of the ethanol effect by compounds affecting the poly‐PI signaling pathway.

Original languageEnglish
Pages (from-to)401-405
Number of pages5
JournalAlcoholism: Clinical and Experimental Research
Volume17
Issue number2
DOIs
StatePublished - Apr 1993

Keywords

  • Acute Ethanol
  • Atropine
  • Cerebellum
  • Cerebrum
  • Poly‐PI Turnover

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