Tetrodotoxin puffer

Tetrodotoxin is one of the most powerful non-protein neurotoxins known. It occurs in the liver and ovaries of the Japanese puffer fish, Sphoerides rubripes and S. phyreus, and its lethal effects have been known for centuries, although it was isolated in crystalline form... 

With respect to toxins which target specific sites, insight can be obtained from the anomolies that are observed. For example, both puffer fish and tetrodotoxin-containing crabs (96) are insensitive to tetrodotoxin. The investigation of such insensitivities can provide information about membrane channels and their toxin binding sites. 

Tetrodotoxin Puffer fish (fugu) Nervous system... 

Puffer fish Fugu spp. Tetrodotoxin (found in Vibrio, Pseudomonas spp.) Alkaloid Predators. Local anesthetic (5-30 minutes) death in 6-24 hours (60% mortality)... 

Pioneering studies were made to determine the structure of tetrodotoxin 1, one of the most toxic compounds among the low-molecular-weight poisons, found in the ovaries and liver of puffer fish, which is a highly esteemed delicacy in Japan. With a combination of the most versatile instrumental facilities, the complex perhydroquinazoline structure of 1 was established (65T2059) in the early 1960s. 

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. 

Japanese puffers of the genus Fugu may, however, be exceptional in this regard because they are able to store saxltoxin (as well as tetrodotoxin) in their livers and gonads (13, 14). 

The variability of toxicity within a particular species with respect to individuals, geographic location, and season (1,40). Decrease in toxicity of eggs of pufferfish during development (41) and the lack of toxicity of cultured pufferfish (42,43). Development of toxicity of non-toxic cultured puffers when fed the livers of toxic wild puffers, but failure to develop toxicity when fed pure tetrodotoxin (42). 

Exogenous Origin. The theory that tetrodotoxin arises in the environment and is ingested by these animals is favored by the finding that cultured puffers are non-toxic. It is also favored by the feeding experiments of Matsui (42), in which non-toxic puffers became toxic upon ingesting toxic livers of wild puffers. The... 

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. 

Fish Puffer fish (fugu) blowfish, toadfish. . . some frogs, starfish, ocopus Tetrodotoxin Nervous system numbness, paralysis, respiratory failure, death Decreased sodium channel permeability... 

Lastly, tetrodotoxin, the Japanese puffer fish toxin, is a polyhydroxylated reduced 2-aminoquinazoline derivative that has attracted a lot of interest, and a number of asymmetric total syntheses have recently been published <2003JA8798, 2003JAl 1510, 2004AGE4782, 2005CRV4537>. 

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) Blocks channel from outside Puffer fish... 

Chemicals, which affect neurons, such as the Puffer fish toxin tetrodotoxin, which blocks voltage-gated Na+ channels in motor neurons, will also affect other cells such as skeletal muscle cells, causing paralysis. 

A variety of toxins that modulate voltage-gated sodium channels have been used to probe channel function. They can be classified on the basis of five discrete binding sites (Table 1). These binding sites are commonly found on all a-subunits and are being characterized at the molecular level. The sensitivity to the puffer fish poison tetrodotoxin (TTX) has been used to subdivide voltage-gated sodium channels (Table 3). 

What is known about the channels through which Na+ and K+ flow during nerve excitation That the channels for the two ions are separate was shown by the fact that tetrodotoxin (found in the puffer fish)429 4293 and saxitoxin of dinoflagellates, as well as... 

Tetrodotoxin, an extremely poisonous heterocycle present in Japanese puffer fish (various species of Spheroides), exerts its action by blocking the sodium ion channels in the peripheral nervous system. Chemically it has an adamantane-like structure, namely octahydro-12 - (hydroxymethyl) - 2 - imino-5,7,9,1 Oa-dimethano- 10aH-[ 1,3] -dioxo-cino-[6,5-d]pyrimidine-4,7,10,11,12-pentol. When chemically dehydrated, it rehydrates in dilute acid.73 Methanol, and ammonia, can add similarly. Because 2-amino-1,6-dihydropyrimidine forms the central part... 

The 1960s saw the discovery of a number of specific channel-blocking agents. Tetrodotoxin, for example, from the fugu puffer fish, specifically blocks voltagegated sodium channels. This provided very convincing confirmation that the sodium and potassium channels of nerve axons really are separate from each other. It also allowed potassium channels in nerves to be studied on their own, permitted estimates of channel densities in the membrane to be made, and ultimately proved crucial in the biochemical isolation of sodium channels. 

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. 

Interspecific differences are also known for some naturally occurring poisons. Nicotine, for instance, is used as an insecticide and kills many insect pests at low doses, yet tobacco leaves constitute a normal diet for several species. As indicated earlier, most strains of rabbit eat Belladonna leaves without ill effects, whereas other mammals are easily poisoned. Natural tolerance to cyanide poisoning in millipedes and the high resistance to the powerful axonal blocking tetrodotoxin in puffer fish are examples of the tolerance of animals to the toxins they produce. 

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