Marine tetrodotoxin

Saxitoxin (STX) is a toxin which is found in marine microorganisms. It is most likely synthesized by bacteria which live in symbiosis with dinoflagellates, a component of phytoplankton. Through the marine food chain, it can lead to poisoning of humans. The mechanism of toxicity of saxitoxin is vety similar to that of tetrodotoxin. Saxitoxin binds from the outside of the membrane to various forms of voltage-sensitive Na+channels and blocks the channel in an activation state-independent manner. 

Tetrodotoxin (TTX) and saxitoxin (STX) are potent sodium channel blockers that are found in phylogenetically diverse species of marine life. The wide distribution of TTX and STX has resulted in speculation that bacteria are the source of these toxins. Recently, investigators have reported isolation of marine bacteria, including Vibrio Alteromonas, Plesiomonas, and Pseudomonas species, that produce TTX and STX. This chapter details the methods and results of research to define bacterial sources of TTX and STX. 

Hwang DF, Arakawa O, Saito T, Noguchi T, Simidu U, Tsukamoto K, Shida Y, Hashimoto K. (1988) Tetrodotoxin-producing bacteria from the blue-ringed octopus Octopus Maculosus. Marine Biology 100 327-332. 

Yamamori, K., Nakamura, M., Matsui, T., and Hara, T. J. (1988). Gustatoiy responses to tetrodotoxin and saxitoxin in fish a possible mechanism foravoiding marine toxins. Canadian Journal of Fisheries and Aquatic Science 45,2182-2186. 

Among the marine toxins relevant for human intoxication, tetrodotoxin (TTX) has been known as one of the most potent low-molecular weight neurotoxins. Puffer fish (family Tetraodontidae — the source of the TTX name) were originally thought to be the only animal from which TTX could be isolated. Subsequent works determined that TTX also exists in a large number of other marine organisms of different phylogenic classes e.g. 

Over the last eight years, most of the estimated cases of world-wide poisoning in humans due to the three major kinds of seafood toxins that are found in fresh and unspoiled marine organisms, namely, paralytic shellfish poison (PSP-saxitoxins/ gonyautoxins), ciguatoxin(s), and tetrodotoxin, (13-16) were caused by ciguatera (Table I). 

A mouse bioassay method is useful for screening of the toxicity of various organisms from affected areas, although this method may not be sufficient for the identification of the toxin. Recently, distribution of tetrodotoxin in the marine ecosystem has expanded from puffer-fishes to some other animals. Rapid and accurate determination of the toxin occurring in those organisms is becoming increasingly important from the public health standpoint. 

The puffer fish is probably the best known neurotoxic fish. Several related species of fish, as well as other marine life, such as some frogs, starfish, octopus, and others, contain tetrodotoxin. Many people consider this fish a delicacy despite the occasional death from poor preparation. Tetrodotoxin is heat stable but water soluble, so careful preparation is necessary to limit neurological effects. Symptoms of poisoning include a rapid onset of numbness in the lips and mouth, which then extends to the fingers and toes, followed by general weakness, dizziness, and respiratory failure, leading to death. The mechanism of action is similar to that of saxitoxin and affects sodium channel permeability. 

Tetrodotoxin/pheromon e and toxin, T12.3.1I alkal. OH (-)-tetrodotoxin marine Bact. and Dinofl. Kodama 1996 puffers land newts and fi ogs (possibly fi-om symbiotic Bact.)... 

Tetrodotoxin (TTX, 1) is one of the best known marine toxins and exhibits potent neurotoxicity by specifically blocking the sodium channels of excitable cell membranes. The etiology of TTX has been an interesting topic because of the wide distribution of the toxin among genetically... 

Saxitoxin has been labeled with fluorescamine, o-phthaldialdehyde (OPA) and dansyl chloride and detection limits as low as 0.1 attomole were reported for the OPA derivative of saxitoxin (26). Labeling, separation, and analysis of saxitoxin was best accomplished using fluorescamine, which produces ionic derivatives that can be separated from other fluorescently labeled marine toxins, such as tetrodotoxin and microcystin. However, the precolumn labeling methods required xM concentrations of analyte, limiting the utility of the technique for trace analysis. 

Marine dinoflagellates produce a number of toxins, such as saxitoxin, surugatoxin, tetrodotoxin, and gonyautoxin, that affect ion channels (Table IV). These algae are eaten by some copepods, fish, and molluscs that also store these neurotoxins 4,17,28,29,494,495). As a consequence, these animals have acquired chemical defense compounds, which they can use against predators. 

Tetrodotoxin has a wide distribution among marine organisms, and a bacterial origin has been postulated (198). In the octopus Hapalochlaena... 

Saxitoxin is a naturally occurring toxin that is synthesized by various marine dinoflagellates. It is used in neurochemical and molecular biology research. Saxitoxin causes paralytic shellfish poisoning. It is far more potent than the classic puffer fish toxin, tetrodotoxin. Saxitoxin is one of only two naturally occurring schedule 1 chemical warfare agents (the other is ricin). 

The extreme toxic potential of marine metabolites often prevents their application in medicine. However, a number of metabolites proved to be valuable tools in biochemistry, cell and molecular biology. For instance the neurotoxic maitotoxin [109-112] (interaction with extracellular calcium enhancement of calcium influx [113]), the neurotoxic brevetoxin B [114] (interaction with the binding-site-5 of voltage-sensitive sodium channels [115]), tetrodotoxin and saxitoxin (voltage clamp analysis to study sodium channels and excitatory phenomena [116] tetrodotoxin abolishes brevetoxin B activity [117]), okadaic acid [118-120] (analysis of phosphorylation and dephosphorylation processes in eukaryotic cell metabolism [121]), and palytoxin (stimulation of arachidonic acid metabolism synergistically with TPA-type promoters [122]). 

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