Activation of Glutamate Receptors Inhibits Na/K-ATPase of Cerebellum Granule Cells

E. R. Bulygina^*, L. Yu. Lyapina, and A. A. Boldyrev

International Training Center of Biotechnology (Department of Biochemistry, School of Biology) and Center for Molecular Medicine, Lomonosov Moscow State University, Moscow, 119992 Russia; fax: (095) 939-1398; E-mail: erb2000@mail.ru

^* To whom correspondence should be addressed.

Received August 1, 2001; Revision received February 6, 2002

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Na/K-ATPase prepared from cerebellum granule cells of 10-12-day-old mice is inhibited by glutamate and its agonists, NMDA (ligand for ionotropic receptors) and ACPD (ligand for metabotropic receptors). The inhibition is specific and prevented by subsequent antagonists (MK-801 for ionotropic NMDA-receptors and MCPG for metabotropic receptors). The inhibiting effect of NMDA is significantly reversed by cysteine and that of ACPD by chelerythrine or indolyl maleimide. It is concluded that ionotropic receptors inhibit Na/K-ATPase because of intracellular production of reactive oxygen species, and metabotropic receptors mediate their effect via protein kinase C.

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KEY WORDS: Na/K-ATPase, cerebellum granule cells, glutamate receptors, reactive oxygen species, oxidative stress, protein kinase C

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