Interactions of neurotoxins with non-NMDA glutamate receptors : an autoradiographic study
Neurotoxic substances are discussed to cause neurodegeneration by acting as excitotoxins on glutamate receptors. We investigated the properties of L-beta-oxalyl-amino-alanine (L-BOAA) and 3,4, 6-trihydroxyphenlyalanine (6-OH-Dopa) at the alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) glutamate receptor and that of L-BOAA and domoic acid at the kainate glutamate receptor in human hippocampus. (3H)AMPA binding in hippocampal subfields was inhibited by L-BOAA and 6-OH-Dopa with mean IC50-values in the low micromolar range. (3H)Kainate binding was inhibited by L-BOAA with similar potency as (3H)AMPA binding and by domoic acid with mean IC50-values in the low nanomolar range. These results support the notion that symptoms like anterograde amnesia and epileptic seizures seen in domoic acid intoxication and limbic symptoms, e.g. cognitive and mood impairment observed in neurolathyrism may be caused by excitotoxic action on non-NMDA receptors. The potent interaction of 6-OH-Dopa with the AMPA-receptor may point to a possible dopaminergic-glutamatergic interaction in the development of neurodegenerative diseases like Parkinson's and Huntington's disease.
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
1994 |
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| Erschienen: |
1994 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:43 |
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| Enthalten in: |
Journal of neural transmission. Supplementum - 43(1994) vom: 01., Seite 59-62 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Künig, G [VerfasserIn] |
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| Anmerkungen: |
Date Completed 13.04.1995 Date Revised 16.11.2017 published: Print Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM075099624 |
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| 041 | |a eng | ||
| 100 | 1 | |a Künig, G |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Interactions of neurotoxins with non-NMDA glutamate receptors |b an autoradiographic study |
| 264 | 1 | |c 1994 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ohne Hilfsmittel zu benutzen |b n |2 rdamedia | ||
| 338 | |a Band |b nc |2 rdacarrier | ||
| 500 | |a Date Completed 13.04.1995 | ||
| 500 | |a Date Revised 16.11.2017 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Neurotoxic substances are discussed to cause neurodegeneration by acting as excitotoxins on glutamate receptors. We investigated the properties of L-beta-oxalyl-amino-alanine (L-BOAA) and 3,4, 6-trihydroxyphenlyalanine (6-OH-Dopa) at the alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) glutamate receptor and that of L-BOAA and domoic acid at the kainate glutamate receptor in human hippocampus. (3H)AMPA binding in hippocampal subfields was inhibited by L-BOAA and 6-OH-Dopa with mean IC50-values in the low micromolar range. (3H)Kainate binding was inhibited by L-BOAA with similar potency as (3H)AMPA binding and by domoic acid with mean IC50-values in the low nanomolar range. These results support the notion that symptoms like anterograde amnesia and epileptic seizures seen in domoic acid intoxication and limbic symptoms, e.g. cognitive and mood impairment observed in neurolathyrism may be caused by excitotoxic action on non-NMDA receptors. The potent interaction of 6-OH-Dopa with the AMPA-receptor may point to a possible dopaminergic-glutamatergic interaction in the development of neurodegenerative diseases like Parkinson's and Huntington's disease | ||
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a Amino Acids, Diamino |2 NLM | |
| 650 | 7 | |a Neurotoxins |2 NLM | |
| 650 | 7 | |a Receptors, AMPA |2 NLM | |
| 650 | 7 | |a Receptors, Glutamate |2 NLM | |
| 650 | 7 | |a Receptors, Kainic Acid |2 NLM | |
| 650 | 7 | |a beta-Alanine |2 NLM | |
| 650 | 7 | |a 11P2JDE17B |2 NLM | |
| 650 | 7 | |a oxalyldiaminopropionic acid |2 NLM | |
| 650 | 7 | |a 1TG777QI25 |2 NLM | |
| 650 | 7 | |a 6-hydroxydopa |2 NLM | |
| 650 | 7 | |a 21373-30-8 |2 NLM | |
| 650 | 7 | |a Dihydroxyphenylalanine |2 NLM | |
| 650 | 7 | |a 63-84-3 |2 NLM | |
| 650 | 7 | |a alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid |2 NLM | |
| 650 | 7 | |a 77521-29-0 |2 NLM | |
| 650 | 7 | |a domoic acid |2 NLM | |
| 650 | 7 | |a M02525818H |2 NLM | |
| 650 | 7 | |a Kainic Acid |2 NLM | |
| 650 | 7 | |a SIV03811UC |2 NLM | |
| 700 | 1 | |a Niedermeyer, B |e verfasserin |4 aut | |
| 700 | 1 | |a Krause, F |e verfasserin |4 aut | |
| 700 | 1 | |a Hartmann, J |e verfasserin |4 aut | |
| 700 | 1 | |a Deckert, J |e verfasserin |4 aut | |
| 700 | 1 | |a Ransmayr, G |e verfasserin |4 aut | |
| 700 | 1 | |a Heinsen, H |e verfasserin |4 aut | |
| 700 | 1 | |a Beckmann, H |e verfasserin |4 aut | |
| 700 | 1 | |a Riederer, P |e verfasserin |4 aut | |
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| 773 | 1 | 8 | |g volume:43 |g year:1994 |g day:01 |g pages:59-62 |
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