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Cardiac glycosides ouabain and digoxin interfere with the regulation of glutamate transporter GLAST in astrocytes cultured from neonatal rat brain

Journal Article


Abstract


  • Abstract Glutamate transport (GluT) in brain is mediated chiefly by two transporters GLT and GLAST, both driven by ionic gradients generated by (Na?, K?)-dependent ATPase (Na?/K?-ATPase). GLAST is located in astrocytes and its function is regulated by translocations from cytoplasm to plasma membrane in the presence of GluT substrates. The phenomenon is blocked by a naturally occurring toxin rottlerin. We have recently suggested that rottlerin acts by inhibiting Na?/K?-ATPase. We now report that Na?/K?-ATPase inhibitors digoxin and ouabain also blocked the redistribution of GLAST in cultured astrocytes, however, neither of the compounds caused detectable inhibition of ATPase activity in cell-free astrocyte homogenates (rottlerin inhibited app. 80% of Pi production from ATP in the astrocyte homogenates,

    IC50 = 25 lM). Therefore, while we may not have established a direct link between GLAST regulation and

    Na?/K?-ATPase activity we have shown that both ouabain and digoxin can interfere with GluT transport and therefore should be considered potentially neurotoxic.

UOW Authors


  •   Nguyen, Khoa T D. (external author)
  •   Buljan, Vlado (external author)
  •   Else, Paul
  •   Pow, David V. (external author)
  •   Balcar, Vladimir J. (external author)

Publication Date


  • 2010

Citation


  • Nguyen, K. T D., Buljan, V., Else, P., Pow, D. V. & Balcar, V. J. (2010). Cardiac glycosides ouabain and digoxin interfere with the regulation of glutamate transporter GLAST in astrocytes cultured from neonatal rat brain. Neurochemical Research, 35 (12), 2062-2069.

Scopus Eid


  • 2-s2.0-78651297072

Ro Metadata Url


  • http://ro.uow.edu.au/hbspapers/3465

Number Of Pages


  • 7

Start Page


  • 2062

End Page


  • 2069

Volume


  • 35

Issue


  • 12

Place Of Publication


  • http://springerlink.metapress.com/content/1j8r28h812740011/fulltext.pdf

Abstract


  • Abstract Glutamate transport (GluT) in brain is mediated chiefly by two transporters GLT and GLAST, both driven by ionic gradients generated by (Na?, K?)-dependent ATPase (Na?/K?-ATPase). GLAST is located in astrocytes and its function is regulated by translocations from cytoplasm to plasma membrane in the presence of GluT substrates. The phenomenon is blocked by a naturally occurring toxin rottlerin. We have recently suggested that rottlerin acts by inhibiting Na?/K?-ATPase. We now report that Na?/K?-ATPase inhibitors digoxin and ouabain also blocked the redistribution of GLAST in cultured astrocytes, however, neither of the compounds caused detectable inhibition of ATPase activity in cell-free astrocyte homogenates (rottlerin inhibited app. 80% of Pi production from ATP in the astrocyte homogenates,

    IC50 = 25 lM). Therefore, while we may not have established a direct link between GLAST regulation and

    Na?/K?-ATPase activity we have shown that both ouabain and digoxin can interfere with GluT transport and therefore should be considered potentially neurotoxic.

UOW Authors


  •   Nguyen, Khoa T D. (external author)
  •   Buljan, Vlado (external author)
  •   Else, Paul
  •   Pow, David V. (external author)
  •   Balcar, Vladimir J. (external author)

Publication Date


  • 2010

Citation


  • Nguyen, K. T D., Buljan, V., Else, P., Pow, D. V. & Balcar, V. J. (2010). Cardiac glycosides ouabain and digoxin interfere with the regulation of glutamate transporter GLAST in astrocytes cultured from neonatal rat brain. Neurochemical Research, 35 (12), 2062-2069.

Scopus Eid


  • 2-s2.0-78651297072

Ro Metadata Url


  • http://ro.uow.edu.au/hbspapers/3465

Number Of Pages


  • 7

Start Page


  • 2062

End Page


  • 2069

Volume


  • 35

Issue


  • 12

Place Of Publication


  • http://springerlink.metapress.com/content/1j8r28h812740011/fulltext.pdf