AR-R15896AR blocks the early NMDA-induced loss of MAP2 in primary cortical cultures.
The low-affinity use-dependent N-methyl-D-aspartate (NMDA) receptor antagonist AR-R15896AR is neuroprotective in primary rat cortical cultures exposed to toxic concentrations of NMDA and reduces the magnitude of NMDA-triggered increases in [Ca2+]i. Here we show using fluorescence staining and measurements of microtubule-associated protein-2 (MAP2) levels, that AR-R15896AR inhibits the NMDA-induced loss of MAP2 that occurs within 2 min following NMDA exposure. Understanding the multiple, Ca(2+)-triggered intracellular events that occur following NMDA receptor stimulation is important to the development of safe and effective neuroprotective agents.
Laferrière
N B
NB
Institute for Biological Sciences, National Research Council of Canada, Ottawa, Ontario.
Tremblay
R
R
Murray
C L
CL
Monette
R
R
Brown
D L
DL
Durkin
J P
JP
Morley
P
P
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001923:Brain Chemistry / Q000187:drug effects*; D020013:Calcium Signaling / Q000187:drug effects*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004353:Drug Evaluation, Preclinical; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D000927:Anticonvulsants; D007476:Ionophores; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D011725:Pyridines; D016194:Receptors, N-Methyl-D-Aspartate; C096406:alpha-phenyl-2-pyridineethanamine dihydrochloride; D015759:Ionomycin; D011189:Potassium Chloride