Glufosinate binds N-methyl-d-aspartate receptors and increases neuronal network activity in vitro

Lantz, Stephen R.; Mack, Cina M.; Wallace, Kathleen; Key, Ellen F.; Shafer, Timothy J.; Casida, John E.

doi:10.1016/j.neuro.2014.09.003

Cited by 35 publications

(18 citation statements)

References 68 publications

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“…One of the most outstanding studies in this field was reported by Lantz et al. 10 Based on the results of an elegantly designed experiment, they concluded that glufosinate bound the N -methyl- d -aspartate receptor, which is a subtype of glutamate receptor, causing stimulation of neuronal network activity. A combination of clinical studies and in vitro studies has provided a growing consensus that seizure is a common complication of glufosinate herbicide intoxication.…”

Section: Introductionmentioning

confidence: 99%

Seizures in patients with acute pesticide intoxication, with a focus on glufosinate ammonium

et al. 2017

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The incidence and clinical aspects of seizures remain to be elucidated in patients with acute pesticide intoxication. The present study included subjects who ingested pesticide with the intention of committing suicide and were treated at Soonchunhyang University Hospital (Cheonan, Korea) between January 2011 and December 2014. We analyzed the incidence and characterized the type and frequency of seizure, from the medical records of 464 patients with acute pesticide intoxication, according to the pesticide class. The effect of seizure on the clinical outcome was assessed. The incidence of seizure was 31.5% in patients who ingested glufosinate ammonium {2-amino-4-[hydroxyl (methyl) phosphinoyl] butyrate; ammonium DL-homoalanin-4-yl (methyl) phosphinate}, followed by those who ingested pyrethroid (5.9%) or glycine derivatives (5.4%). All of the seizures developed between 12 and 24 h of pesticide ingestion and had ceased by 72 h after seizure initiation, following treatment with antiseizure medication. Generalized tonic-clonic seizures were the most commonly observed (85.7% of the cases). Multivariable logistic regression analysis showed that the effect of seizure on mortality was not statistically significant. In conclusion, glufosinate ammonium herbicide is the most common seizurogenic pesticide class. Seizure itself was not a risk factor for mortality in patients with acute glufosinate ammonium intoxication.

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Section: Introductionmentioning

confidence: 99%

Seizures in patients with acute pesticide intoxication, with a focus on glufosinate ammonium

et al. 2017

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“…Glufosinate, a methyl phosphonate analog of glutamate, causes excitotoxic cell death and moderate to severe neurotoxicity, including convulsions and memory loss in the brain [27,28].…”

Section: Discussionmentioning

confidence: 99%

Acute glufosinate-based herbicide treatment in rats leads to increased ocular interleukin-1β and c-Fos protein levels, as well as intraocular pressure

et al. 2019

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“…L-PPT is an aminoacid structurally related to glutamate. It was demonstrated that L-PPT binds with L-[ 3 H]-glutamate labelling sites in rat brain plasma membranes (Fagg and Lanthorn 1985) and N-methyl-d-aspartate receptors (Lantz et al 2014). Studies in animal models show that NMDA receptor antagonists markedly inhibited the convulsions induced by L-PPT, suggesting that L-PPT effects can be mediated through a stimulation of NMDA receptors with consequent production of NO (Nakaki et al 2000;Lapouble et al 2002).…”

Section: Discussionmentioning

confidence: 99%

L-Phosphinothricin modulation of inwardly rectifying K+ channels increased excitability in striatal medium-sized spiny neurons

et al. 2016

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Phosphinotricin (L-PPT) is the active compound of a broad-spectrum herbicide. Acute poisoning with L-PPT has various clinical manifestations, including seizures and convulsions. However, the exact mechanism of L-PPT toxicity remains unclear. The present study addressed the role of L-PPT, in the excitability of striatal medium-sized spiny neurons (MSNs). In whole-cell current-clamp experiments, L-PPT increased the input resistance (Ri), decreased the rheobase and increased the firing frequency of action potentials. In voltage-clamp experiments, L-PPT inhibited the inward-rectifying potassium (Kir) currents. Finally, the effects of L-PPT mimicked the inhibition of Kir channels with Ba(2+) on neuronal excitability. Altogether, these results suggest that the herbicide L-PPT is a modulator of Kir channels in MSNs. Thereby, Kir channels are potent regulators of the excitability of MSNs and reduced open probability of these channels would generate a powerful upregulation of neuronal output. This effect may represent a possible mechanism for L-PPT dependent neuronal toxicity.

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Glufosinate binds N-methyl-d-aspartate receptors and increases neuronal network activity in vitro

Cited by 35 publications

References 68 publications

Seizures in patients with acute pesticide intoxication, with a focus on glufosinate ammonium

Seizures in patients with acute pesticide intoxication, with a focus on glufosinate ammonium

Acute glufosinate-based herbicide treatment in rats leads to increased ocular interleukin-1β and c-Fos protein levels, as well as intraocular pressure

L-Phosphinothricin modulation of inwardly rectifying K+ channels increased excitability in striatal medium-sized spiny neurons

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