TY - JOUR
T1 - The NMDA receptor agonist DL-(tetrazol-5-yl) glycine is a highly potent excitotoxin
AU - Schoepp, Darryle D.
AU - Lunn, William H.W.
AU - Salhoff, Craig R.
AU - McDonald, John W.
PY - 1994/1/3
Y1 - 1994/1/3
N2 - DL-(Tetrazol-5-yl)glycine is a highly selective N-methyl-D-aspartate (NMDA) receptor agonist with nanomolar in vitro potency. Previous work showed that DL-(tetrazol-5-yl)glycine has greater affinity and efficacy at NMDA receptors than other NMDA receptor agonists such as cis-methanoglutamate and NMDA. In this study, the in vivo excitotoxic potency of DL-(tetrazol-5-yl)glycine was compared to cis-methanoglutamate and NMDA. Adult (250-300 g) and neonatal (7-day-old) rats were anesthetized and compounds were unilaterally injected into the striatum. In adult rats DL-(tetrazol-5-yl)glycine (0.3-1.0 nmol/μl) produced highly significant losses of striatal γ-aminobutyric acid neurons (as indexed by glutamic acid decarboxylase activity) and cholinergic neurons (as indexed by choline acetyltransferase activity). Dose-response showed that DL-(tetrazol-5-yl)glycine was about 100 and 500 times more potent than cis-methanoglutamate and NMDA, respectively. In neonatal rats, DL-(tetrazol-5-yl)glycine (0.1-0.3 nmol/μl) produced significant brain damage as indicated by brain weight losses 5 days later. DL-(Tetrazol-5-yl)glycine was about 50 and 150 times more potent than cis-methanoglutamate and NMDA, respectively, in the neonate. The excitotoxic potency of DL-(tetrazol-5-yl)glycine is likely due to its greater efficacy and potency at the NMDA receptor, when compared to other NMDA receptor agonists. The remarkable in vivo potency of DL-(tetrazol-5-yl)glycine in producing excitotoxic lesions makes it a useful agent to further probe NMDA receptor mediated ecitotoxicity in brain pathologies.
AB - DL-(Tetrazol-5-yl)glycine is a highly selective N-methyl-D-aspartate (NMDA) receptor agonist with nanomolar in vitro potency. Previous work showed that DL-(tetrazol-5-yl)glycine has greater affinity and efficacy at NMDA receptors than other NMDA receptor agonists such as cis-methanoglutamate and NMDA. In this study, the in vivo excitotoxic potency of DL-(tetrazol-5-yl)glycine was compared to cis-methanoglutamate and NMDA. Adult (250-300 g) and neonatal (7-day-old) rats were anesthetized and compounds were unilaterally injected into the striatum. In adult rats DL-(tetrazol-5-yl)glycine (0.3-1.0 nmol/μl) produced highly significant losses of striatal γ-aminobutyric acid neurons (as indexed by glutamic acid decarboxylase activity) and cholinergic neurons (as indexed by choline acetyltransferase activity). Dose-response showed that DL-(tetrazol-5-yl)glycine was about 100 and 500 times more potent than cis-methanoglutamate and NMDA, respectively. In neonatal rats, DL-(tetrazol-5-yl)glycine (0.1-0.3 nmol/μl) produced significant brain damage as indicated by brain weight losses 5 days later. DL-(Tetrazol-5-yl)glycine was about 50 and 150 times more potent than cis-methanoglutamate and NMDA, respectively, in the neonate. The excitotoxic potency of DL-(tetrazol-5-yl)glycine is likely due to its greater efficacy and potency at the NMDA receptor, when compared to other NMDA receptor agonists. The remarkable in vivo potency of DL-(tetrazol-5-yl)glycine in producing excitotoxic lesions makes it a useful agent to further probe NMDA receptor mediated ecitotoxicity in brain pathologies.
KW - DL-(Tetrazol-5-yl)glycine
KW - Excitotoxicity
KW - NMDA (N-methyl-D-aspartate)
KW - Neurodegeneration
KW - cis-Methanoglutamate
UR - http://www.scopus.com/inward/record.url?scp=0028177949&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0028177949&partnerID=8YFLogxK
U2 - 10.1016/0926-6917(94)90081-7
DO - 10.1016/0926-6917(94)90081-7
M3 - Article
C2 - 8157082
AN - SCOPUS:0028177949
SN - 0926-6917
VL - 270
SP - 67
EP - 72
JO - European Journal of Pharmacology: Environmental Toxicology and
JF - European Journal of Pharmacology: Environmental Toxicology and
IS - 1
ER -