Glutamate receptors communicate with Na+/K+-ATPase in rat cerebellum granule cells: demonstration of differences in the action of several metabotropic and ionotropic glutamate agonists on intracellular reactive oxygen species and the sodium pump.
Two glutamate receptor agonists, NMDA (N-methyl-D-aspartic acid) and ACPD (cis-(1S/3R)-1-aminocyclopentane- 1,3-dicarboxylic acid), induce the reactive oxygen species (ROS) production 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 can be demonstrated: NMDA and ACPD inhibited the enzyme activity, but 3-HPG activated Na+/K+-ATPase and prevented its inhibition by NMDA or ACPD. In terms of current classification, NMDA is an agonist of ionotropic glutamate receptors of the so-called NMDA class, whereas ACPD and 3-HPG belong to metabotropic agonists, the former primarily being an activator of metabotropic glutamate receptors (mGluRs) of groups 2 and 3, and the latter, that of mGluRs of groups 1 and 5. Thus, 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.
Boldyrev
Alexander
A
Center for Molecular Medicine and International Biotechnological Center of M V Lomonosov Moscow State University (Department of Biochemistry), Lenin's Hills, 119992 Moscow, Russia. aaboldyrev@mail.ru
Bulygina
Elena
E
Carpenter
David
D
Schoner
Wilhelm
W
D000818:Animals; D002478:Cells, Cultured; D002525:Cerebellar Cortex / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D004148:Dioxolanes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005456:Fluorescent Dyes / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000201:enzymology*; D011687:Purines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D004148:Dioxolanes; D018690:Excitatory Amino Acid Agonists; D005456:Fluorescent Dyes; D011687:Purines; D017382:Reactive Oxygen Species; D017470:Receptors, Glutamate; D018094:Receptors, Metabotropic Glutamate; C078245:4-carboxy-3-hydroxyphenylglycine; C104068:4-(2-amino-6-chloro-9H-purin-9-yl)-1,3-dioxolane-2-methanol; D016202:N-Methylaspartate; D000254:Sodium-Potassium-Exchanging ATPase; D005998:Glycine