Homocysteic and homocysteine sulphinic acid exhibit excitotoxicity in organotypic cultures from rat brain.
The excitotoxic action of homocysteine and related sulphur-containing metabolites was investigated in organotpyic cultures derived from rat brain cortex and hippocampus by inhibition experiments using antagonists selective for different glutamate receptor subtypes. In addition the direct interaction of these metabolites with glutamate receptors expressed in frog oocytes was tested by conventional two electrode voltage clamp techniques.


CONCLUSIONS
Neurodegeneration and epilepsy observed in homocystinuria may be mediated by L-homocysteic and L-homocysteine sulphinic acid. Both metabolites exhibit excitotoxic potency by interaction with different glutamate receptor subtypes.
Flott-Rahmel
B
B
Department of Paediatrics, University Hospital of Muenster, Germany.
Schürmann
M
M
Schluff
P
P
Fingerhut
R
R
Musshoff
U
U
Fowler
B
B
Ullrich
K
K
D000818:Animals; D000831:Animals, Newborn; D016923:Cell Death; D002540:Cerebral Cortex / Q000187:drug effects*; D004594:Electrophysiology; D006624:Hippocampus / Q000187:drug effects*; D006710:Homocysteine / Q000378:metabolism*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D051381:Rats; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism*; D013441:Sulfinic Acids / Q000494:pharmacology*; D014982:Xenopus laevis
D017470:Receptors, Glutamate; D013441:Sulfinic Acids; D006710:Homocysteine