Tetrodotoxin concentration

No risk factors for tetrodotoxin poisoning are known. It is likely that intoxication and its severity are dose dependent [137], Age has not been shown to increase the risk of illness in Taiwan, illness occurred in persons from 9 months to 71 years of age [137]. The toxin is heat stable so that cooking is not protective. Tetrodotoxin concentrates in the viscera and roe of some animals, such as puffer fish [148], Presumably,... 

Matsumura, K. (1996) Tetrodotoxin concentrations in cultured puSer fish, Fugu rubripes. J. Agric. Food Chem.. 44,1-2. 

Tetrodotoxin (TTX) is a toxin derived from bacteria which is concentrated in the gonads and liver of certain pufferfishes (fugu). Similar to saxitoxin, tetrodotoxin is a very potent blocker of most voltage-sensitive Na+ channels. 

PTX caused a dose-dependent release of norepinephrine (NE). The NE release induced by lower concentrations of PTX increased proportionately with increasing Na concentrations, but was not modified by tetrodotoxin. However, the NE-releasing action of higher concentrations of PTX was dependent on external Ca, but not Na . Thus our experimental results suggest that in adrenergic neurons the PTX-induced release of NE by lower concentrations of PTX is brought about by tetrodotoxin-insensitive Na permeability, whereas that induced by higher concentrations is mainly caused by a direct increase of Ca influx into smooth muscle cells. 

Na and Ca Influx. PTX caused a concentration-dependent increase in Na and Ca influxes into PC12 cells at concentrations of 10" to 10" M and 10" to 10" M, respectively. The PTX-induced Ca influx was markedly inhibited by Co but not by verapamil or nifedepine, whereas the PTX-induc Na influx was not affected by tetrodotoxin. 

Physiological studies show that monensin is a sodium ionophore (15), that induces inotropic effect on guinea pig atria (17). The polyether toxins including ciguatoxin, okadaic acid, and the recently characterized brevetoxin (5, 16) also induce inotropic effect on guinea pig atrial tissue in vitro (17). Additionally, partially purified CTX has been implicated in the depolarization of nerve cells in vitro, which can be reversed by high concentrations of Ca tetrodotoxin and saxitoxin (18). 

Exogenous. Tetrodotoxin is not produced by the animal but arises from the food chain in some manner, for instance, similar to the way saxitoxin is concentrated by shellfish that ingest the toxic Gonyaulax dinoflagellates. 

The ability of tetrodotoxin-containing animals to tolerate a concentration of tetrodotoxin in their bodies that would be fatal to other animals and the resistance of these animals to administration of tetrodotoxin (44-46). 

Apart from AP-A, the best characterized of these polypeptides with respect to its biological activity is Anemonia sulcata toxin II (ATX II) [19]. This molecule is also cardioactive [28], as would be expected from its similarity to AP-A. Renaud et al. [29] have compared the activities of a number of sea anemone and scorpion toxins on isolated rat atria and found that anthopleurin-B (AP-B, also known as Ax II) had the highest potency and the greatest margin between the concentrations necessary for maximal inotropic activity and for provoking arrhythmias (0.3 versus 10 n . It was also found that sodium channels of rat cardiac cells in culture, which have a low affinity for tetrodotoxin (TTX), have a particularly high affinity for Type 1 anemone toxins [29], whereas Type 2 toxins [30] and scorpion toxins [31] had similar affinities for TTX-sensitive and TTX-insensitive channels in rat neuroblastoma cells and skeletal myotubes, respectively. 

Many fish species, over 700 species worldwide, are either directly toxic or upon ingestion are poisonous to humans. A classic example is the toxin produced by the puffer fishes (Sphaeroides spp.) called tetrodotoxin (TTX). Tetrodotoxin is concentrated in the gonads, liver, intestine, and skin, and poisonings occurs most frequently in Japan and other Asian countries where the flesh, considered a delicacy, is eaten as fugu. Death occurs within 5 to 30 minutes and the fatality rate is about 60%. TTX is an inhibitor of the voltage-sensitive Na channel (like saxitoxin) it may also be found in some salamanders and may be bacterial in origin. 

In vivo microdialysis is a technique that allows sampling of extracellular levels of neurotransmitters in discrete regions of the brain. The extracellular neurotransmitter levels provide an indication of the net activity of a particular set of neurons, including release, synthesis, and uptake, from conscious unanesthetized animals. For example, in vivo microdialysis studies have shown that extracellular 5-HT levels measured under appropriate conditions are dependent on the concentration of Ca2+ or K+ in the perfusion fluid, is inhibited by tetrodotoxin, and is predominately neuronal in origin (45). In addition, specific neural processes can be measured after the local application of agents through the microdialysis probe, such as release after application of hypertonic KC1, rate of synthesis after synthesis inhibitors, or the local effects of drugs (46). This technique has made it possible to more accurately quantitate and characterize the... 

Fig. 2.14. Hymenotepis diminuta effects of calcium and cobalt on contractions of the longitudinal musculature in strips of tissue cut from the adult worm. In normal Ringer s solution, periodic contractions of the longitudinal muscles were generated spontaneously (a) and (6). (a) Tetrodotoxin (TTX, 5 x 10 6 M) did not affect spontaneously generated muscle contractions. The application of CoCl2 (5 x 10 3 m) resulted in sustained muscle contractions. (6) The application of CaCl2 (5 x 10 3 m) caused muscle relaxation (final calcium concentration 6.2x 10 3M).CoC12(5 x 10 3 M) elicited sustained contraction. Acetylcholine (ACh, 5 x 10 4 M) caused relaxation. (After Thompson Mettrick, 1984.)...

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. 

Cells carefully control the homeostasis of their ion concentrations by the action of ion channels (Na, K , Ca " channels) and throu Na, K -ATPase and Ca -ATPase. These channels and pumps are involved in signal transduction, active transport processes, and neuronal and neuromuscular signaling. Inhibition of transport processes (ion channels, carriers) is achieved by (Table IV) acronycine, ervatamine, harmaline, quinine, reserpine, colchicine, nitidine, salsolinol, sanguinarine, stepholidine, caffeine, sparteine, monocrotaline, steroidal alkaloids, aconitine, capsaicine, cassaine, maitoxin, ochratoxin, palytoxin, pumiliotoxin, saxitoxin, sole-nopsine, and tetrodotoxin. 

Exposure occurs through ingestion of flesh, viscera (e.g., liver, gonads), or skin containing tetrodotoxin. The viscera contain the highest concentration. 

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