Demonstration of differences in the action of several metabotropic and ionotropic glutamate agonists on intracellular reactive oxygen species and the Na-pump
A. Boldyrev (1), E. Bulygina (1), D. Carpenter (2) and W. Schoner (3)
1 - M.V. Lomonosov Moscow State University (Department of Biochemistry), Lenin's Hills, 119992 Moscow, Russia; 2 - University at Albany, Renssellaer, NY 12144-3456, USA; 3 - University of Giessen, D-35392 Giessen, Germany
Two glutamate receptor agonists, NMDA (N-methyl-D-aspartic acid) and
ACPD (cis-(1S/3R)-1-aminocyclopentane-1,3-dicarboxylic acid) increase
the reactive oxygen species (ROS) level in rat cerebellum granule cells
whereas the third one, 3-HPG (3-hydroxyphenylglycine) decreases this
parameter. The simultaneous presence of 3-HPG together with NMDA or
ACPD prevents the generation of ROS by neuronal cells. A similar effect
of these ligands on Na/K-ATPase was demonstrated: NMDA and ACPD
inhibited the enzyme activity but 3-HPG activated Na/K-ATPase and
prevented its inhibition by NMDA or ACPD. NMDA is known as an agonist
of ionotropic glutamate receptors, whereas ACPD and 3-HPG belong to
metabotropic agonists, the former mostly being an activator of
metabotropic receptors of groups (2+3) and the latter that of groups
(1+5). The data presented illustrate the existence of diverse
mechanisms of the cross-talk between Na/K-ATPase and different
glutamate receptors as well as that between glutamate receptors of
different classes. Moreover, 3-HPG-activated metabotropic receptors
protect the neurons against excitotoxic effects induced by ACPD- and
NMDA-activated receptors.
Key words:
glutamate receptors, reactive oxygen species, Na-pump
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