Regional differences in the interaction of the excitotoxins domoate and L-beta-oxalyl-amino-alanine with [3H]kainate binding sites in human hippocampus.
The excitotoxic amino acid domoate causes anterograde amnesia and memory deficits while the excitotoxin L-beta-oxalyl-amino-alanine (L-BOAA) is considered the causative agent of the motoneurone disorder, neurolathyrism. Employing quantitative autoradiography we investigated the potency of domoate and L-BOAA to inhibit [3H]kainate binding in human hippocampus. Domoate inhibited binding of [3H]kainate with inhibition constants between 5.8 +/- 2.8 nM (deep layers of gyrus parahippocampalis) and 200.9 +/- 247.8 nM (CA1 region of hippocampus). It was about a thousandfold more potent than L-BOAA with inhibition constants between 2.1 +/- 0.5 microM (superficial layers of gyrus parahippocampalis) and 51.0 +/- 41.9 microM (CA2/3 region of hippocampus). Interestingly, L-BOAA showed lowest affinity to [3H]kainate binding sites in those regions in which domoate showed highest affinity (e.g. CA2/3) and vice versa (e.g. CA1). These data further support the notion that the neurological symptoms observed after domoate intoxication are due to an excitotoxic action at kainate receptors and provide evidence for heterogeneity of kainate receptors in human hippocampus.
Künig
G
G
Department of Clinical Neurochemistry, University of Würzburg, Germany.
Hartmann
J
J
Krause
F
F
Deckert
J
J
Heinsen
H
H
Ransmayr
G
G
Beckmann
H
H
Riederer
P
P
D000368:Aged; D000599:Amino Acids, Diamino; D001345:Autoradiography; D001665:Binding Sites / Q000187:drug effects; D002102:Cadaver; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D007608:Kainic Acid / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D009498:Neurotoxins / Q000494:pharmacology; D015091:beta-Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology
D000599:Amino Acids, Diamino; D009498:Neurotoxins; D015091:beta-Alanine; C100126:oxalyldiaminopropionic acid; C012301:domoic acid; D007608:Kainic Acid