Cardiac Glycosides Ouabain and Digoxin Interfere with the Regulation of Glutamate Transporter GLAST in Astrocytes Cultured from Neonatal Rat Brain |
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Authors: | Nguyen Khoa T D Buljan Vlado Else Paul L Pow David V Balcar Vladimir J |
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Institution: | (1) Discipline of Anatomy and Histology, School of Medical Sciences, Bosch Institute of Biomedical Research, Sydney Medical School, The University of Sydney, Anderson Stuart Building F 13, Sydney, NSW 2006, Australia;(2) Metabolic Research Centre and School of Health Sciences, University of Wollongong, Wollongong, NSW, 2522, Australia;(3) Centre for Clinical Research, Royal Brisbane and Women’s Hospital, The University of Queensland, Brisbane, QLD, 4029, Australia; |
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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. |
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