Isodomoic acids A and C exhibit low KA receptor affinity and reduced in vitro potency relative to domoic acid in region CA1 of rat hippocampus.

Isodomoic acids A and C exhibit low KA receptor affinity and reduced in vitro potency relative to domoic acid in region CA1 of rat hippocampus. Research Abstract Details 

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Isodomoic acids A and C exhibit low KA receptor affinity and reduced in vitro potency relative to domoic acid in region CA1 of rat hippocampus. Abstract Text:

P M Sawant,B A Weare,P T Holland,A I Selwood,K L King,C M Mikulski,G J Doucette,D O Mountfort,D S Kerr,P M Sawant,B A Weare,P T Holland,A I Selwood,K L King,C M Mikulski,G J Doucette,D O Mountfort,D S Kerr,

Several natural isomers of the seizurogenic neurotoxin domoic acid (DA) have been found to occur at up to mg/kg levels in shellfish. The aim of the current study was to assess the neurotoxic potency of isodomoic acids A and C (Iso-A and Iso-C), recently isolated from commercial shellfish. Hippocampal slices were obtained from young adult rats and maintained in a tissue recording chamber. Synaptically evoked population spikes were recorded in region CA1 before and after exposure to DA or its isomers. Both Iso-A and Iso-C produced transient neuronal hyperexcitability followed by a dose-dependent suppression of population spikes, but were, respectively, 4- and 20-fold less potent than DA (spike area: EC50 DA=237 nM; Iso-A=939 nM; Iso-C=4.6 microM). In the hippocampus, DA preconditioning induces tolerance to subsequent DA toxicity. However, in the present study neither Iso-A nor Iso-C were effective as preconditioning agents. Competitive binding studies using homomeric GluR6 kainate (kainic acid, KA) receptors showed the affinity of Iso-A to be 40-fold lower than DA (Ki DA=3.35 nM; Iso-A=130 nM). Together with earlier work showing Iso-C affinity at GluR6 receptors to be 240-fold lower than DA, our results suggest that neuroexcitatory effects of Iso-A in CA1 may involve both alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) and KA receptors, while Iso-C likely involves the activation of AMPA receptors alone.

Isodomoic acids A and C exhibit low KA receptor affinity and reduced in vitro potency relative to domoic acid in region CA1 of rat hippocampus. Publishing Authors By Initials

PM Sawant,BA Weare,PT Holland,AI Selwood,KL King,CM Mikulski,GJ Doucette,DO Mountfort,DS Kerr,PM Sawant,BA Weare,PT Holland,AI Selwood,KL King,CM Mikulski,GJ Doucette,DO Mountfort,DS Kerr,

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Isodomoic acids A and C exhibit low KA receptor affinity and reduced in vitro potency relative to domoic acid in region CA1 of rat hippocampus. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Toxicon : official journal of the International So

VOLUME: 50

Page Numbers: 627-38

Journal Abbreviation: Toxicon

ISSN: 0041-0101

DAY: 8

MONTH: 06

YEAR: 2007

Isodomoic acids A and C exhibit low KA receptor affinity and reduced in vitro potency relative to domoic acid in region CA1 of rat hippocampus. Information

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LANGUAGE: eng

NlmUniqueID: 1307333

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Grant and Affiliation Information for Isodomoic acids A and C exhibit low KA receptor affinity and reduced in vitro potency relative to domoic acid in region CA1 of rat hippocampus.

AFFILIATION: Department of Pharmacology and Toxicology, University of Otago School of Medical Sciences, P.O. Box 913, Dunedin, New Zealand.

Country: England

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MEDLINETA: Toxicon

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