Reduced neuroexcitatory effect of domoic acid following mossy fiber denervation of the rat dorsal hippocampus: further evidence that toxicity of domoic acid involves kainate receptor activation

1989 ◽  
Vol 67 (8) ◽  
pp. 904-908 ◽  
Author(s):  
Guy Debonnel ◽  
Michel Weiss ◽  
Claude de Montigny
Keyword(s):  
Kainic Acid ◽  
Prince Edward Island ◽  
Domoic Acid ◽  
Pyramidal Neurons ◽  
Mossy Fiber ◽  
Excitatory Amino Acid ◽  
Dorsal Hippocampus ◽  
Receptor Activation ◽  
Kainate Receptors ◽  
Quisqualic Acid

Domoic acid, an excitatory amino acid structurally related to kainic acid, has been shown to be responsible for the severe intoxication presented, in 1987, by more than one hundred and fifty people having eaten mussels grown in Prince Edward Island (Canada). Unitary extracellular recordings were obtained from pyramidal neurons of the CA3 region of the rat dorsal hippocampus. The excitatory effects of microiontophoretic applications of domoic acid and of the agonists of the two other subtypes of glutamatergic receptors, quisqualate and N-methyl-D-aspartate, were compared on intact and colchicine-lesioned sides. Similar to what has been previously found for kainate, the colchicine lesion of the mossy fiber projections induced a 95% decrease of the neuronal responsiveness to domoic acid, whereas the effect of quisqualate was unchanged and that of N-methyl-D-aspartate was only slightly decreased. These results provide further electrophysiological evidence that domoic acid is a potent agonist of kainate receptors and that it may produce its neuroexcitatory and neurotoxic effects, in the hippocampal CA3 region, through activation of kainate receptors located on the mossy fiber terminals.Key words: domoic acid, kainic acid, glutamic acid, N-methyl-D-aspartic acid, quisqualic acid, dorsal hippocampus, neurotoxins.

Domoic acid, the alleged "mussel toxin," might produce its neurotoxic effect through kainate receptor activation: an electrophysiological study in the rat dorsal hippocampus

1989 ◽  
Vol 67 (1) ◽  
pp. 29-33 ◽  
Author(s):  
Guy Debonnel ◽  
Luc Beauchesne ◽  
Claude de Montigny
Keyword(s):  
Amino Acid ◽  
Domoic Acid ◽  
Pyramidal Neurons ◽  
Excitatory Amino Acid ◽  
Dorsal Hippocampus ◽  
Electrophysiological Study ◽  
Receptor Activation ◽  
Kainate Receptor ◽  
Neurotoxic Effect ◽  
Excitatory Effect

Domoic acid, an excitatory amino acid structurally related to kainate, was recently identified as being presumably responsible for the recent severe intoxication presented by more than 100 people having eaten mussels grown in Prince Edward Island (Canada). The amino acid kainate has been shown to be highly neurotoxic to the hippocampus, which is the most sensitive structure in the central nervous system. The present in vivo electrophysiological studies were undertaken to determine if domoic acid exerts its neurotoxic effect via kainate receptor activation. Unitary extracellular recordings were obtained from pyramidal neurons of the CA1 and the CA3 regions of the rat dorsal hippocampus. The excitatory effect of domoic acid applied by microiontophoresis was compared with that of agonists of the three subtypes of glutamatergic receptors: kainate, quisqualate, and N-methyl-D-aspartate. In CA1, the activation induced by domoic acid was about threefold greater than that induced by kainate; identical concentrations and similar currents were used. In CA3, domoic acid was also three times more potent than kainate. However, the most striking finding was that domoic acid, similar to kainate, was more than 20-fold more potent in the CA3 than in the CA1 region, whereas no such regional difference could be detected with quisqualate and N-methyl-D-aspartate. As the differential regional response of CA1 and CA3 pyramidal neurons to kainate is attributable to the extremely high density of kainate receptors in the CA3 region, these results provide the first electrophysiological evidence that domoic acid may produce its neurotoxic effects through kainate receptor activation.Key words: domoate, kainate, excitotoxin, hippocampus, N-methyl-D-aspartate.

scholarly journals Marine Excitatory Amino Acids: Structure, Properties, Biosynthesis and Recent Approaches to Their Syntheses

Molecules ◽  
2020 ◽  
Vol 25 (13) ◽  
pp. 3049 ◽  
Author(s):  
Valentin A. Stonik ◽  
Inna V. Stonik
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Glutamate Receptors ◽  
Excitatory Amino Acids ◽  
Domoic Acid ◽  
Excitatory Amino Acid ◽  
Biological Action ◽  
Kainate Receptors ◽  
Marine Metabolites ◽  
Structure Properties

This review considers the results of recent studies on marine excitatory amino acids, including kainic acid, domoic acid, dysiherbaine, and neodysiherbaine A, known as potent agonists of one of subtypes of glutamate receptors, the so-called kainate receptors. Novel information, particularly concerning biosynthesis, environmental roles, biological action, and syntheses of these marine metabolites, obtained mainly in last 10–15 years, is summarized. The goal of the review was not only to discuss recently obtained data, but also to provide a brief introduction to the field of marine excitatory amino acid research.

Pharmacology of systemically administered domoic acid in mice

1991 ◽  
Vol 69 (3) ◽  
pp. 378-382 ◽  
Author(s):  
R. A. R. Tasker ◽  
B. J. Connell ◽  
S. M. Strain
Keyword(s):  
Kainic Acid ◽  
Dose Response ◽  
Domoic Acid ◽  
Rating Scale ◽  
Excitatory Amino Acid ◽  
Shellfish Poisoning ◽  
Response Curves ◽  
Toxic Dose ◽  
Dose Response Curves

Domoic acid, a structural analogue of kainic acid, has been identified as the toxin that poisoned people who consumed contaminated blue mussels harvested from eastern Prince Edward Island in December of 1987. To investigate the pharmacology of domoic acid in vivo we injected groups of mice with serial dilutions of extracts of contaminated mussels and verified domoic acid concentrations using high performance liquid chromatography. Mice progressed through a series of behavioural changes that were both reproducible and dose-dependent. These behaviours formed the basis of a rating scale that was used to reliably quantitate domoic acid concentrations as low as 20 μg/mL. This scale was then used to compare the relative toxicity of domoic acid contained in four formulations: namely, (1) extracts of contaminated mussels, (2) pure domoic acid, (3) extracts of noncontaminated mussels that were "spiked" with pure domoate, and (4) extracts of the algal source of domoic acid. Interpolation of the resulting dose–response curves produced median toxic dose (TD50) values of 2.9, 3.9, 4.9, and 4.2 mg/kg for the four formulations, respectively. Statistical analysis of these data revealed that curves for all formulations of domoic acid were parallel, but that extracts of contaminated mussels were significantly more potent than any of the other formulations at low and intermediate doses of domoic acid. We further compared domoic acid toxicity with that produced by kainic acid. Dose–response curves for both compounds were statistically parallel and both toxins were equally efficacious. The TD50 values were 3.9 and 31.9 mg/kg for pure domoic acid and kainic acid, respectively. We conclude that this method can be effectively applied to studies of domoic acid pharmacology in vivo and that domoic acid is 8 – 11 times more potent than kainic acid following systemic administration.Key words: domoic acid, domoate, kainic acid, excitatory amino acid, amnesic shellfish poisoning.

scholarly journals Dopamine D1 receptor activation regulates sodium channel-dependent EPSP amplification in rat prefrontal cortex pyramidal neurons

2007 ◽  
Vol 581 (3) ◽  
pp. 981-1000 ◽  
Author(s):  
Diana C. Rotaru ◽  
David A. Lewis ◽  
Guillermo Gonzalez-Burgos
Keyword(s):  
Prefrontal Cortex ◽  
Sodium Channel ◽  
Pyramidal Neurons ◽  
Receptor Activation ◽  
Dopamine D1 Receptor ◽  
D1 Receptor ◽  
Channel Dependent

scholarly journals A kainic acid receptor from frog brain purified using domoic acid affinity chromatography.

1988 ◽  
Vol 263 (5) ◽  
pp. 2500-2505
Author(s):  
D R Hampson ◽  
R J Wenthold
Keyword(s):  
Affinity Chromatography ◽  
Kainic Acid ◽  
Domoic Acid ◽  
Acid Receptor ◽  
Frog Brain

Domoic acid enhances the K+-evoked release of endogenous glutamate from guinea pig hippocampal mossy fiber synaptosomes

1991 ◽  
Vol 551 (1-2) ◽  
pp. 303-307 ◽  
Author(s):  
David M. Terrian ◽  
Teresa A. Conner-Kerr ◽  
Thomas H. Privette ◽  
Robert L. Gannon
Keyword(s):  
Guinea Pig ◽  
Domoic Acid ◽  
Mossy Fiber

scholarly journals Ethanol Enhances Neurosteroidogenesis in Hippocampal Pyramidal Neurons by Paradoxical NMDA Receptor Activation

2011 ◽  
Vol 31 (27) ◽  
pp. 9905-9909 ◽  
Author(s):  
K. Tokuda ◽  
Y. Izumi ◽  
C. F. Zorumski
Keyword(s):  
Nmda Receptor ◽  
Pyramidal Neurons ◽  
Receptor Activation ◽  
Hippocampal Pyramidal Neurons ◽  
Nmda Receptor Activation

Glutamate Neurotransmission Is Not Required for, But May Modulate, Hypoxic Sensitivity of Pre-Bötzinger Complex In Vivo

2005 ◽  
Vol 93 (3) ◽  
pp. 1278-1284 ◽  
Author(s):  
Irene C. Solomon
Keyword(s):  
Phrenic Nerve ◽  
Excitatory Amino Acid ◽  
Glutamate Release ◽  
Receptor Activation ◽  
Motor Output ◽  
Induced Response ◽  
Homocysteic Acid ◽  
Bötzinger Complex ◽  
Nerve Discharge

Focal hypoxia in the pre-Bötzinger complex (pre-BötC) in vivo elicits excitation of inspiratory motor output by modifying the patterning and timing of phrenic bursts. Hypoxia, however, has been reported to enhance glutamate release in some regions of the brain, including the medullary ventral respiratory column; thus the pre-BötC–mediated hypoxic respiratory excitation may result from, or be influenced by, hypoxia-induced activation of ionotropic glutamate [i.e., excitatory amino acid (EAA)] receptors. To test this possibility, the effects of focal pre-BötC hypoxia [induced by sodium cyanide (NaCN)] were examined before and after blockade of ionotropic EAA receptors [using kynurenic acid (KYN)] in this region in chloralose-anesthetized, vagotomized, mechanically ventilated cats. Before blockade of ionotropic EAA receptors, unilateral microinjection of NaCN (1 mM; 10–20 nl) into the pre-BötC produced either phasic or tonic excitation of phrenic nerve discharge. Unilateral microinjection of KYN (50–100 mM; 40 nl) decreased the amplitude and frequency of basal phrenic nerve discharge; however, subsequent microinjection of NaCN, but not dl-homocysteic acid (DLH, a glutamate analog), still produced excitation of phrenic motor output. Under these conditions, the NaCN-induced excitation included frequency modulation (FM) of phasic phrenic bursts, and in many cases, augmented and/or fractionated phrenic bursts. These findings show that the hypoxia-sensing function of the in vivo pre-BötC, which produces excitation of phrenic nerve discharge, is not dependent on activation of ionotropic glutamate receptors, but ionotropic glutamate receptor activation may modify the expression of the focal hypoxia-induced response. Thus these findings provide additional support to the concept of intrinsic hypoxic sensitivity of the pre-BötC.

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