Phosphinothricin induces epileptic activity via nitric oxide production through NMDA receptor activation in adult mice.
Phosphinothricin (PPT), the active component of a widely used herbicide, induces convulsions in rodents and humans. PPT shares structural analogy with glutamate, which could explain its powerful inhibitory effect on glutamine synthetase and its probable binding to glutamate receptors. To characterize the epileptogenic effect of PPT, electrographic and behavioural studies were carried out on PPT-treated adult mice. We investigated the role of N-methyl-D-aspartate (NMDA) receptor activation and nitric oxide (NO) production in induction of seizures triggered by PPT, by using specific NMDA antagonist and nitric oxide synthase (NOS) inhibitor. The inhibitory effect of PPT on glutamine synthetase of mouse brain was assessed after in vitro and in vivo treatments. The results obtained show that PPT induces tonic-clonic seizures and generalized convulsions in mice. They suggest that these seizures are mediated through an NMDA receptor activation and NO production, without involvement of inhibition of glutamine synthetase.
Lapouble
Eve
E
Laboratoire du Métabolisme Cérébral et Neuropathologies (MCN), UPRES 2633, Université d'Orléans, avenue du parc floral, BP 6759, 45 067 Orléans cedex 2, France.
Montécot
Céline
C
Sevestre
Aurélie
A
Pichon
Jacques
J
D000613:Aminobutyrates / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004569:Electroencephalography; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004827:Epilepsy / Q000139:chemically induced* / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000378:metabolism*; D012640:Seizures / Q000139:chemically induced
D000613:Aminobutyrates; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D009569:Nitric Oxide; C003121:phosphinothricin; D016291:Dizocilpine Maleate; D005974:Glutamate-Ammonia Ligase