Excitotoxins L-beta-oxalyl-amino-alanine (L-BOAA) and 3,4,6-trihydroxyphenylalanine (6-OH-DOPA) inhibit [3H] alpha-amino-3- hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) binding in human hippocampus.
Excitotoxins L-beta-oxalyl-amino-alanine (L-BOAA) and 3,4,6-trihydroxyphenylalanine (6-OH-DOPA) have been investigated with regard to their potency to inhibit [3H] alpha-amino-3-hydroxy-5-methyl-4- isoxazole-propionic acid (AMPA) binding in human hippocampus in a quantitative autoradiographic study. With dissociation constants (KD) of [3H]AMPA binding and inhibition concentrations (IC50) of L-BOAA, 6-OH-DOPA and L-glutamate obtained from saturation and displacement experiments inhibition constants (Ki) for the inhibition of [3H]AMPA binding in individual hippocampal subregions could be calculated. They were between 5.2 +/- 2.9 and 35.1 +/- 39.9 microM for L-BOAA and 39.1 +/- 26.8 and 59.4 +/- 44.1 microM for 6-OH-DOPA. L-BOAA was equally potent as the endogenous agonist L-glutamate with Ki's between 13.1 +/- 3.9 and 21.4 +/- 12.1 microM (n = 4, mean +/- S.D.). Limbic system symptoms like cognitive deficits, mood disturbances and vivid dreams observed in patients with the motor neuron disease neurolathyrism may thus well be mediated by agonistic action of L-BOAA at AMPA glutamate receptors in hippocampus.
Künig
G
G
Department of Neurochemistry, University of Würzburg, FRG.
Hartmann
J
J
Niedermeyer
B
B
Deckert
J
J
Ransmayr
G
G
Heinsen
H
H
Beckmann
H
H
Riederer
P
P
D000368:Aged; D000369:Aged, 80 and over; D000599:Amino Acids, Diamino; D001345:Autoradiography; D001667:Binding, Competitive / Q000187:drug effects; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors*; D015091:beta-Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology
D000599:Amino Acids, Diamino; D005971:Glutamates; D018091:Receptors, AMPA; D015091:beta-Alanine; C100126:oxalyldiaminopropionic acid; C001388:6-hydroxydopa; D018698:Glutamic Acid; D004295:Dihydroxyphenylalanine