Rough-skin newts (Taricha granulosa) released tetrodotoxin (TTX) in their skin secretions in response to mild electric stimulation. This release resulted in a large (21% to almost 90% of the pre-stimulation levels) reduction in the amount of TTX present in the dorsal skin of individual newts. Over the next 9 months newts significantly regenerated the levels of TTX in their skin. These data, in combination with previously published results, are consistent with the hypothesis that these newts produce their own TTX.

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http://dx.doi.org/10.1016/j.toxicon.2004.09.006DOI Listing

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Introduction: One of the most important emerging infectious diseases of amphibians is caused by the fungal pathogen . was recently discovered and is of global concern due to its potential to cause high mortality in amphibians, especially salamander species. To date, little has been reported on the pathophysiological effects of ; however, studies of a similar fungus, , have shown that electrolyte losses and immunosuppression likely play a key role in morbidity and mortality associated with this disease.

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The origin and biogenesis of tetrodotoxin (TTX) is one of the most interesting and perplexing questions remaining for TTX researchers. Newts can possess extreme quantities of TTX and are one of the most well-studied of all TTX-bearing organisms, yet seemingly conflicting results between studies on closely related species continues to generate debate. In this study, eggs from 12 female newts (Taricha granulosa) were reared in captivity and the metamorphosed juveniles were fed a TTX-free diet for 3 years.

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Rough-skinned newts, Taricha granulosa, which contain tetrodotoxin (TTX), a potent neurotoxin, are widely distributed along the west-coast of North America up to British Columbia (BC), Canada, and Southeast Alaska. Their genetic population structure using DNA-microsatellites and the TTX-content of specimens from British Columbia (Prince Rupert area) and Alaska (Revillagigedo Island, Shelter Island, and Juneau) were analysed. TTX-concentrations were low in newts from BC and Revillagigedo Island, but high in specimens from mainland Juneau, which had been deliberately introduced from Shelter Island, where TTX was not detectable in the individuals sampled.

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The biosynthesis of the potent neurotoxin tetrodotoxin (TTX, ) is still unresolved. We used MS-guided screening and nuclear magnetic resonance analyses including long-range HSQMBC to characterize two novel skeletal tricyclic guanidino compounds, Tgr-288 ( and ) and Tgr-210 (), from the TTX-bearing newt, . The presence of these compounds in toxic newts is congruent with a previously proposed pathway for TTX biosynthesis in terrestrial organisms that includes a monoterpene precursor and the production of structurally diversified guanidino compounds.

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