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Cardiac glycosides ouabain and digoxin interfere with the regulation of glutamate transporter GLAST in astrocytes cultured from neonatal rat brain.
Nguyen, Khoa T D; Buljan, Vlado; Else, Paul L; Pow, David V; Balcar, Vladimir J.
  • Nguyen KT; 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.
Neurochem Res ; 35(12): 2062-9, 2010 Dec.
Article en En | MEDLINE | ID: mdl-20890657
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.
Asunto(s)

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Ouabaína / Encéfalo / Astrocitos / Transportador 1 de Aminoácidos Excitadores / Digoxina Límite: Animals Idioma: En Año: 2010 Tipo del documento: Article

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Ouabaína / Encéfalo / Astrocitos / Transportador 1 de Aminoácidos Excitadores / Digoxina Límite: Animals Idioma: En Año: 2010 Tipo del documento: Article