L-homocysteic acid mediates synaptic excitation at NMDA receptors in the hippocampus.
beta-p-Chlorophenylglutamate (Chlorpheg), a specific L-homocysteate (L-HC) uptake blocker, was tested on the L-HC- and L-glutamate-induced currents and on the excitatory postsynaptic potentials (EPSPs) evoked in CA1 rat hippocampal neurons by Schaffer collaterals stimulation. In the presence of tetrodotoxin (TTX; 1 microM), Chlorpheg (0.5-2 mM) potentiated L-HC- but not L-glutamate-induced currents. In normal magnesium containing medium and at resting membrane potential, Chlorpheg (1.5-1 mM) increased the amplitude and duration of the EPSPs evoked by Schaffer collaterals stimulation. This effect was prevented by bath application of the N-methyl-D-aspartate (NMDA) receptor antagonist CPP (20 microM). Chlorpheg enhanced also the NMDA component of the EPSP, evoked in the presence of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 10 microM), bicuculline (20 microM) and glycine (100 microM). This effect was blocked by CPP (20 microM). It is concluded that L-HC is an endogenous NMDA agonist at the Schaffer collateral-CA1 synapse.
INSERM Unité 29, Paris, France.
S
S
Ito
L
L
Provini
E
E
Cherubini
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects; D005971:Glutamates / Q000494:pharmacology*; D005998:Glycine / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D006710:Homocysteine / Q000031:analogs & derivatives* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology
D005971:Glutamates; D010879:Piperazines; D011810:Quinoxalines; D016194:Receptors, N-Methyl-D-Aspartate; D006710:Homocysteine; C007956:homocysteic acid; D013779:Tetrodotoxin; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; C045418:3-(4-chlorophenyl)glutamic acid; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; D005998:Glycine; D001640:Bicuculline