Nitric oxide in retina: relation to excitatory amino acids and excitotoxicity.
This study was undertaken to determine whether nitric oxide pathways exist in the retina and are linked to excitatory amino acid (EAA)-induced increases in cyclic guanosine monophosphate (cGMP). Exposure of embryonic day 15 chick retina for 5 min to either 1 mM glutamate, 100 microM NMDA or 100 microM kainate (KA) increased cGMP content 2-3-fold. The putative environmental neurotoxins, domoic acid (DO, 20 microM), and beta-oxalyl-amino-L-alanine (BOAA, 200 microM), but not beta-methyl-amino-L-alanine (BMAA, 3 mM), also increased cGMP. The nitric oxide synthase inhibitor N-nitro-L-arginine (NNA) and nitric oxide scavenger, hemoglobin, completely blocked the increases in cGMP induced by the above glutamate-agonists. These glutamate agonist induced increases in cGMP were receptor mediated. MK-801, a NMDA receptor antagonist, blocked NMDA, and partially blocked glutamate-stimulated, cGMP formation. CNQX, a KA/AMPA receptor antagonist blocked cGMP increases produced by KA, BOAA and partially blocked those evoked by DO and glutamate. In order to examine the involvement of nitric oxide pathways in NMDA-mediated toxicity, the ability of NNA to protect against delayed excitotoxic damage caused by a 60 min exposure to NMDA was assessed. Delayed cell death, determined by LDH release and histology, following a 24 hr recovery period after NMDA treatment, was unchanged by the presence of NNA. NNA did not interfere with acute NMDA-stimulated GABA release indicating that NNA did not effect NMDA receptor interactions.(ABSTRACT TRUNCATED AT 250 WORDS)
Zeevalk
G D
GD
Department of Neurology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School 08854.
Nicklas
W J
WJ
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D016923:Cell Death; D002642:Chick Embryo; D006152:Cyclic GMP / Q000378:metabolism; D005971:Glutamates / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D016202:N-Methylaspartate / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D017470:Receptors, Glutamate / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D012160:Retina / Q000033:anatomy & histology / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D005971:Glutamates; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D019335:Nitroarginine; D009569:Nitric Oxide; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; D001120:Arginine; D007770:L-Lactate Dehydrogenase; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D006152:Cyclic GMP