beta-N-methylamino-L-alanine is a low-affinity agonist of metabotropic glutamate receptors.
beta-N-methylamino-L-alanine (L-BMAA) is an excitotoxin whose neurodegenerative effects are associated with its agonist properties at the N-methyl-D-aspartate (NMDA) receptor. We measured the effects of L-BMAA on inositol phosphate (InsP) formation in primary cultured striatal neurons. This culture is almost devoid of glial cells and the pharmacology of glutamate receptors is well-defined. This allowed us to show that L-BMAA induced InsP formation via a direct action at the glutamate metabotropic (Qp) receptors coupled to InsP formation. We demonstrated that L-BMAA is a full-agonist of the Qp receptor, but with a low potency. Therefore, the neurotoxic properties of L-BMAA might implicate the activation of the Qp receptor in association with the NMDA receptor.
Centre CNRS-INSERM de Pharmacologie-Endocrinologie, Montpellier, France.
O J
OJ
Manzoni
L
L
Prezeau
J
J
Bockaert
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000599:Amino Acids, Diamino / Q000494:pharmacology*; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D000087522:Cyanobacteria Toxins; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004622:Embryo, Mammalian; D005971:Glutamates / Q000502:physiology; D007294:Inositol / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism*; D007700:Kinetics; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009498:Neurotoxins / Q000494:pharmacology*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*
D000599:Amino Acids, Diamino; D000087522:Cyanobacteria Toxins; D005971:Glutamates; D007295:Inositol Phosphates; D009498:Neurotoxins; D011810:Quinoxalines; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D003515:Cycloleucine; C001824:beta-N-methylamino-L-alanine; C036361:1-amino-1,3-dicarboxycyclopentane; D015240:Phorbol 12,13-Dibutyrate; D007294:Inositol; D016291:Dizocilpine Maleate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D002217:Carbachol