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

Nguyen, Ktd, Buljan, V, Else, PL, Pow, DV and Balcar, VJ (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. doi:10.1007/s11064-010-0274-4


Author Nguyen, Ktd
Buljan, V
Else, PL
Pow, DV
Balcar, VJ
Title Cardiac glycosides ouabain and digoxin interfere with the regulation of glutamate transporter GLAST in astrocytes cultured from neonatal rat brain
Journal name Neurochemical Research   Check publisher's open access policy
ISSN 0364-3190
1573-6903
Publication date 2010-12
Sub-type Article (original research)
DOI 10.1007/s11064-010-0274-4
Volume 35
Issue 12
Start page 2062
End page 2069
Total pages 8
Place of publication New York, NY, United States
Publisher Springer New York LLC
Collection year 2011
Language eng
Formatted 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 μM). 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.
© 2010 The Author(s).
Keyword Na+/K+-ATPase
Rottlerin
Ouabain
Digoxin
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2011 Collection
 
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Created: Sun, 23 Jan 2011, 00:02:38 EST