Specific antagonism of excitotoxic action of ‘uncommon’ amino acids assayed in organotypic mouse cortical cultures

Ross, Stephen M.; Seelig, Mary; Spencer, Peter S.

doi:10.1016/0006-8993(87)90490-2

Cited by 154 publications

(46 citation statements)

References 21 publications

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“…The main mechanism of neurotoxicity of L-BMAA has been reported to be a receptor agonist of glutamate (Ross et al, 1987;Chiu et al, 2012). However, exactly how it causes neuronal death is not well understood.…”

Section: Discussionmentioning

confidence: 99%

β-N-methylamino-L-alanine induces changes in both GSK3 and TDP-43 in human neuroblastoma

et al. 2013

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Section: Discussionmentioning

confidence: 99%

β-N-methylamino-L-alanine induces changes in both GSK3 and TDP-43 in human neuroblastoma

et al. 2013

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“…5,6) L-b -ODAP behaved as a potent agonist at AMPA receptors that were constructed by a 1 homomeric (Ca 2ϩ permeable) or a 1 /a 2 heteromeric (not Ca 2ϩ permeable) receptor clones with potency comparable to L-glutamate. 5) Ross et al 7) showed that antagonists to non-NMDA receptors prevented neuronal degeneration by L-b -ODAP in organotypic cortical cultures. Weiss et al 8) described the neuron-specific toxicity of L-b -ODAP and a related compound, b-N-methylamino-L-alanine, on cultured mouse cortical neurons.…”

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confidence: 99%

Partial Involvement of Group I Metabotropic Glutamate Receptors in the Neurotoxicity of 3-N-Oxalyl-L-2,3-diaminopropanoic Acid (L-.BETA.-ODAP)

Kusama-Eguchi

Kusama

Suda

et al. 2004

Biological & Pharmaceutical Bulletin

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The non-protein amino acid L-b -ODAP (3-N-oxalyl-L-2,3-diaminopropanoic acid, or its synonym b-N-oxalylamino-Lalanine, BOAA) has been proposed as a causative agent of the crippling disease termed neurolathyrism.1,2) This is a human upper motoneuron disease disabling the legs of patients who had eaten grass pea (Lathyrus sativus L.) seeds for a substantial period of time as a major food source in some Asian and African countries.3) L-b -ODAP is one of the major free amino acids of this draught-tolerant legume. As the etiology of neurolathyrism is still not well understood, it is of primary importance to understand the molecular mechanism inducing this upper motoneuron disease with sudden onset.By in vitro studies, Bridges et al. 4) first demonstrated that Ross et al. 7) showed that antagonists to non-NMDA receptors prevented neuronal degeneration by L-b -ODAP in organotypic cortical cultures. Weiss et al. 8) described the neuron-specific toxicity of L-b -ODAP and a related compound, b-N-methylamino-L-alanine, on cultured mouse cortical neurons. The former acted on non-NMDA receptors with IC 50 of 20 mM, and the latter on the NMDA receptor with IC 50 of 1 mM. Saroff et al. 9) showed the selective vulnerability of a-motoneurons to non-NMDA agonists quisqualate and kainate using organotypic spinal cord cultures. Recently, the involvement of metabotropic glutamate receptors (mGluRs) on excitotoxicity has been increasingly attracting interest.10-15) Among three groups of mGluR, group I receptors reside in the post-synaptic membrane and accelerate excitatory amino acid (EAA) transmission and sometimes toxicity through the activation of phospholipase C b resulting in [Ca 2ϩ ] i elevation. 12,14) Group II receptors reside extrasynaptically, and negatively regulate glutamatergic neurotransmission. 13,16) Group III receptors are an autoreceptors that reside pre-synaptically and regulate glutamate release by decreasing intracellular cAMP. 17) Therefore, activating group II or III receptors may decrease excitotoxicity in some cases. 17) In fact, several reports concerning group II and group III receptors support this hypothesis. 13,18,19) Considering the complex cascade of reactions that leads to acute neuronal death, the neurolathyrism after the prolonged over-consumption of grass pea seed is not fully explained by the excitation of the AMPA receptors by the inherent natural substance L-b -ODAP. Seeking for some other physiological activity, we have found the potency of this compound on mGluRs using rat primary cortical neuron/glia cultures. Our results show the possibility of this natural toxin to trigger a cascade of reactions leading to acute neuronal death, especially with the activation of one or more mGluRs. MATERIALS AND METHODS Chemicals

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“…The excitotoxic actions of glutamate (Choi, 1987;Rothman et a!., 1987;Lysko et al, 1989;Boje et al, 1993;Platt and Bristow, 1995;Wood and Bristow, 1998) and BMAA Ross et al, 1987;Weiss et a!., 1989;Staton and Bristow, 1997) have been characterised in several neuronal preparations. However, whereas glutamate and BMAA have unequivocal neurotoxic actions, ACPD produces effects ranging from neurotoxicity (Aleppo et al, 1992;McDonald and Schoepp, 1992;Schoepp et al, 1994) to neuroprotection (Koh et al, 1991;Chiamulera et al, 1992;Siliprandi et al, 1992;Pizzi et al, 1993Pizzi et al, , 1996aColwell et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

Role of Group III Metabotropic Glutamate Receptors in Excitotoxin‐Induced Cerebellar Granule Cell Death

Staton

Bristow

1998

Journal of Neurochemistry

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Abstract:The neuronal effects of the metabotropic glutamate receptor agonist (1 S,3R)-aminocyclopentane-1 ,3-dicarboxylic acid have been studied in cultured rat cerebellar granule cells, and compared with those of the endogenous excitotoxin glutamate, and the dietary excitotoxin /3-N-methylamino-L-alanine. Glutamate,~3-N-methylamino-L-alanine, and (1 S ,3R) -aminocyclopentane-1 ,3-dicarboxylic acid all caused concentration-dependent cerebellar granule cell death over a 24-h exposure period. The metabotropic antagonist (RS) -a-methyl-4-carboxyphenylglycine reduced glutamate-, /3-N-methylamino-L-alanine-, and (1 S ,3R)-aminocyclopentane-1 ,3-dicarboxylic acid-induced death by 50, 37, and 90%, respectively. (1 S ,3R) -Aminocyclopentane-1 ,3-dicarboxylic acid-induced death was unaffected by the group I antagonist (RS)-1 -aminoindan-1 ,5-dicarboxylic acid, increased by the group II antagonist ethylglutamic acid, and markedly decreased by the group Ill antagonist (RS) -amethylserine-O-phosphate. Neither (1 S ,3R) -aminocyclopentane-1 ,3-dicarboxylic acid nor the group I agonist (RS)-3,5-dihydroxyphenylglycine caused an increase in intracellular free calcium levels. The group Ill agonist L-(+)-2-amino-4-phosphonobutyric acid also induced concentration-dependent cerebellar granule cell death, and so it was suggested that the group Ill metabotropic glutamate receptors were responsible for (1 S,3R)-aminocyclopentane-1 ,3-dicarboxylic acid-induced death. Blocking these receptors with (RS) -a-methylserine-O-phosphate also prevented a proportion of glutamate-and /3-N-methylamino-L-alanineinduced death. Key Words: (1 S,3R)-Aminocyclopentane-1 ,3-dicarboxylic acid-/3-N-Methylamino-L-alanine-Rat cerebellar granule cells-Glutamate. J. Neurochem. 71, 1280Neurochem. 71, -1288Neurochem. 71, (1998.Glutamate is the principal excitatory neurotransmitter in the mammalian brain, where it activates both ionotropic glutamate receptors and metabotropic glutamate receptors (mGluRs). Tonotropic glutamate receptors are ligand-gated ion channels that comprise NMDA and a-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) kainate subtypes (Monaghan et al., 1989). Overactivation of ionotropic receptors results in neuronal death via excitotoxicity , and some of the intracellular events that lead to death can be influenced by mGluRs (Pin and Duvoisin, 1995).mGluRs are coupled to U proteins, and this family of glutamate receptors comprises eight subtypes, to date, that are divided into three groups, based on their second messenger coupling, sequence similarity, and ligand selectivities (Pin and Duvoisin, 1995). Group I includes mGluRi and mGluR5, which are coupled to polyphosphoinositide (PPI) hydrolysis. mGluRs from groups II (mGluR2 and mGluR3) and III (mGluR4, mGluR6, mGluR7, and mGluR8) are negatively coupled to adenylate cyclase activity. In addition, an mGluR receptor coupled to phospholipase D has been identified in the hippocampus (Pellegrini-Giampetro et al., 1996). This coupling to disparate transduction pathways may underlie th...

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Specific antagonism of excitotoxic action of ‘uncommon’ amino acids assayed in organotypic mouse cortical cultures

Cited by 154 publications

References 21 publications

β-N-methylamino-L-alanine induces changes in both GSK3 and TDP-43 in human neuroblastoma

β-N-methylamino-L-alanine induces changes in both GSK3 and TDP-43 in human neuroblastoma

Partial Involvement of Group I Metabotropic Glutamate Receptors in the Neurotoxicity of 3-N-Oxalyl-L-2,3-diaminopropanoic Acid (L-.BETA.-ODAP)

Role of Group III Metabotropic Glutamate Receptors in Excitotoxin‐Induced Cerebellar Granule Cell Death

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