ABSTRACT

Domoic acid (DA) is a naturally-occurring excitatory amino acid that was identifi ed as the toxin responsible for an outbreak of amnesic shellfi sh poisoning (ASP) that occurred in Canada in 1987 following consumption of contaminated blue mussels (Mytilus edulis) (Perl et al. 1990). Subsequent to that event there have been numerous outbreaks of DA toxicity in a variety of wildlife species including marine invertebrates, various fi sh species, pisciverous birds and several species of marine mammals including California sea lions (Zalophus californianis) and whales (for review see Ch’ng et al. 2002, Lefebvre et al. 2002, Doucette and Tasker 2008). The parent compound is a tricarboxylic amino acid produced by certain marine organisms, the best characterised of which are the red macroalga Chondria armata (Takemoto and Daigo 1960) and various members of the Nitzschia pungens spp. of planktonic diatoms, which serve as the principal vector for toxicity outbreaks (for review see Bates 1998). Domoic acid is closely related structurally and pharmacologically to another kainoid, kainic acid (KA), produced by another red macroalga Digenia simplex (Murakami et al. 1953). The structures of both DA and KA are shown in Fig. 1. Kainic acid is

Department of Biomedical Sciences, University of Prince Edward Island, 550 University Avenue, Charlottetown, PEI, Canada C1A 4P3. Email: tasker@upei.ca

used extensively in neurobiological research for both intracerebral lesioning and as a chemical convulsant (for review see McGeer and McGeer 1981). Pharmacologically both DA and KA are agonists at ionotropic glutamate receptors, having particular affi nity for the AMPA/kainate subclass of these receptors (for review see Bleakman et al. 2002). Consequently the pharmacological and toxicological profi les of both toxins are similar, but not identical because the two toxins have differing selectivity for particular subunits in the AMPA/kainate receptor group (Tasker and Strain 1992, Johansen et al. 1993, Verdoorn et al. 1994, Tasker et al. 1996).