Interaction of some plant heterocyclic beta-substituted alanines with rat brain N-methyl-D-aspartate (NMDA) receptors.
The neuropharmacological actions of some plant heterocyclic beta-substituted alanines on rat brain N-methyl-D-aspartate (NMDA) receptors were studied. Of the compounds tested, 3-N-oxalyl-L-2,3-diaminopropanoic acid (beta-ODAP), the causal agent of human neurolathyrism, exhibited an inhibitory activity on the NMDA receptor binding assay at a relatively high concentration (IC50: 4.7 x 10(-5)M). The biochemical precursor of beta-ODAP, beta-(isoxazolin-5-on-2-yl)-L-alanine (BIA) was inactive in this assay. These results suggest that beta-ODAP, the neurotoxin of Lathyrus sativus, in addition to its excitatory action on alpha-amino-3-hydroxy-5-methylisoxazole-4-propanoic acid (AMPA) receptors, also has neurotoxic potential through its action on NMDA receptors.
Ikegami
F
F
Faculty of Pharmaceutical Sciences, Chiba University, Japan.
Kusama-Eguchi
K
K
Sugiyama
E
E
Watanabe
K
K
Lambein
F
F
Murakoshi
I
I
D000409:Alanine / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000378:metabolism; D006571:Heterocyclic Compounds / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D010944:Plants / Q000737:chemistry*; D011869:Radioligand Assay; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D014316:Tritium
D006571:Heterocyclic Compounds; D016194:Receptors, N-Methyl-D-Aspartate; D014316:Tritium; D016291:Dizocilpine Maleate; D000409:Alanine