Maitotoxin

Abstract Ciguatoxin, scaritoxin, and maitotoxin (MTX) are the marine compounds held responsible for ciguatera poisoning, although the role of MTX is disputed (8). Like ciguatoxin, MTX is produced by the marine dinoflagellate Gambier discus toxicus, and accumulates in the marine food chain in fish in tropical coral reefs. It is infrequently detected in tropical fish and is likely not as important clinically as ciguatoxin. Different strains of the dinoflagellate produce distinct maitotoxins with specific physiological effects (5). In contrast to ciguatoxin, the polyether and highly polar substance MTX (MW of the disodium salt, 3424) (16) is soluble in water, unlikely to cross cellular membranes, and often detected in herbivorous (algae-eating) fish. The name maitotoxin is derived from the Tahitian name of the fish (maito for surgeon fish, Ctenochaetus striatus) from which this chemical was originally isolated (15). Its structure is partly elucidated; it contains a chain with more than 100 carbons, many small ether rings, 21 methyl groups, numerous tertiary amine groups, two sulfate esters, and a basic nitrogen (4). Fish harboring the toxin do not become ill. When injected intraperitoneally into mice, the LD50 of MTX is as low as 0.13 µ,g/kg body weight. Signs of murine poisoning are similar to those produced by ciguatoxin; they include diarrhea, reduced locomotor activity, convulsions, and hypothermia. MTX acts on many cell types, including muscle cells and neurons. MTX dose-dependently increases Ca2+ entry into a wide range of cultured cells at concentrations as low as 100 pM to 30 nM; however, the precise mechanism of Ca2+ influx is controversial and may differ among cell types (3,4,9,12,14). The relative contribution of L-type and N-type voltage-gated Ca2+ channels and the mobilization of Ca2+ from intracellular stores to the consistent, large intracellular increase of Ca2+ concentration, is un known (9,12,14). Other biological, largely Ca2+-dependent effects are stimulation of neurotransmitter and hormone re lease, stimulation of phosphoinositide breakdown; and contraction of smooth, cardiac, and skeletal muscle (4).