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.
reactive oxygen species