Elsevier

Biochemical Pharmacology

Volume 36, Issue 12, 15 June 1987, Pages 2027-2033
Biochemical Pharmacology

Effects of ethanol on ouabain inhibition of mouse brain (Na+,K+)ATPase activity

https://doi.org/10.1016/0006-2952(87)90504-1Get rights and content

Abstract

Plots of ouabain inhibition of mouse cerebral cortical (Na+K+ATPase activity fitted a two-site model significantly better than a one-site model, consistent with the presence of two forms of the enzyme with different affinities for ouabain. The fraction of enzyme activity with high affinity for ouabain (HAO: Ki = 500 nM), suggested to be localized neuronally, constituted the major portion (60–70%) of activity. Ouabain inhibition of both components of enzyme activity was reduced as KC1 concentrations were increased. In vitro, only high concentrations of ethanol affected (Na+,K+)ATPase activity and ouabain inhibition of activity. Ethanol (500 mM) selectively reduced the activity, and increased the sensitivity to ouabain inhibition, of the HAO component, with no significant effect on the low-affinity (LAO) component. On the other hand, following chronic treatment of mice with ethanol in vivo, in a paradigm that produced tolerance and physical dependence, the sensitivity to ouabain of the HAO form of the enzyme was selectively increased. The relative proportions, and the activities of the HAO and LAO components, were not altered. The effects of ethanol, added in vitro, on the HAO component were decreased in ethanol-tolerant animals. The selective effect of chronic ethanol ingestion on (Na+,K+)ATPase activity indicates the specificity of action of ethanol in the CNS.

References (39)

  • M.J. Marks et al.

    Life Sci.

    (1978)
  • K.J. Sweadner

    J. biol. Chem.

    (1979)
  • S.C. Specht

    Biochem. biophys. Res. Commun.

    (1984)
  • A.C. Swann

    J. biol. Chem.

    (1983)
  • J.S. Charnock et al.

    Biochim. biophys. Acta

    (1977)
  • Y. Israel et al.

    Biochem. Pharmac.

    (1965)
  • Y. Israel et al.

    Archs. Biochem. Biophys.

    (1967)
  • H. Kalant et al.

    Biochem. Pharmac.

    (1978)
  • N. Rangaraj et al.

    Biochem. Pharmac.

    (1978)
  • O.H. Lowry et al.

    J. biol. Chem.

    (1951)
  • M.C. Kohn et al.

    Comput. biomed. Res.

    (1979)
  • Y.R. Choi et al.

    Biochim. biophys. Acta

    (1977)
  • J.S. Charnock et al.

    Archs Biochem. Biophys.

    (1975)
  • R.C. Aloia et al.

    Life Sci.

    (1985)
  • G.Y. Sun et al.

    Life Sci.

    (1984)
  • A.C. Collins et al.

    Alcohol

    (1984)
  • P.T. Nhamburo et al.

    Biochem. Pharmac.

    (1986)
  • H. Kalant et al.

    Eur. J. Pharmac.

    (1981)
  • A.C. Swann

    J. Pharmac. exp. Ther.

    (1984)
  • Cited by (20)

    View all citing articles on Scopus
    View full text