Acute excitotoxicity in chick retina caused by the unusual amino acids BOAA and BMAA: effects of MK-801 and kynurenate.
beta-N-Oxalylamino-L-alanine (BOAA) and beta-N-methylamino-L-alanine (BMAA) were tested for their ability to produce acute excitotoxicity in in embryonic chick retina. gamma-Aminobutyric acid (GABA) release and histology were monitored in retina treated with various concentrations of BOAA, BMAA, kainate (KA), N-methyl-D-aspartate (NMDA), or glutamate. BOAA and BMAA caused retinal lesions similar to those produced by the excitatory amino acids. BOAA was slightly less potent than KA, whereas BMAA had a potency similar to glutamate. BOAA, like KA and NMDA, caused a dose-dependent increase in GABA release. Addition of the NMDA antagonist (+)-MK-801, completely blocked acute excitotoxicity caused by NMDA or BMAA but was ineffective against KA or BOAA. Kynurenate, a nonspecific glutamate receptor antagonist, and DIDS, a Cl- channel blocker, were effective in blocking all agonist-induced toxicity. It is concluded that BOAA and BMAA cause excitotoxic damage in retina; BOAA induces toxicity through a non-NMDA type glutamate receptor and BMAA through the NMDA receptor.
Zeevalk
G D
GD
UMDNJ, Robert Wood Johnson Medical School, Department of Neurology, Piscataway 08854.
Nicklas
W J
WJ
D000599:Amino Acids, Diamino / Q000494:pharmacology*; D000818:Animals; D001224:Aspartic Acid / Q000494:pharmacology; D002642:Chick Embryo; D000087522:Cyanobacteria Toxins; D003986:Dibenzocycloheptenes / Q000494:pharmacology*; D016291:Dizocilpine Maleate; D005971:Glutamates / Q000494:pharmacology; D006651:Histocytochemistry; D007736:Kynurenic Acid / Q000494:pharmacology; D016202:N-Methylaspartate; D009474:Neurons / Q000378:metabolism; D009498:Neurotoxins / Q000494:pharmacology*; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000378:metabolism; D012160:Retina / Q000187:drug effects / Q000378:metabolism*; D015091:beta-Alanine / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000599:Amino Acids, Diamino; D000087522:Cyanobacteria Toxins; D003986:Dibenzocycloheptenes; D005971:Glutamates; D009498:Neurotoxins; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; C001824:beta-N-methylamino-L-alanine; D015091:beta-Alanine; C100126:oxalyldiaminopropionic acid; D001224:Aspartic Acid; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D007736:Kynurenic Acid