Origin of tetrodotoxin and toxification mechanism in tetrodotoxin-bearing pufferfishes and Japanese newt

河豚鱼血浆中含有与河豚毒素(TTX)结合的高分子量物质(TTX结合物质)。血浆中的TTX大部分以与物质结合的状态存在。TTX结合物质不仅能结合TTX，而且还能结合石杉毒素(STX)。血浆中自然存在少量与物质结合的STX。所有受检河豚鱼的血浆均显示TTX结合能力。其中，河豚的血浆活性最强，其1毫升血浆可与23个小鼠单位的河豚毒素结合。河豚毒素结合物质在酸性条件下解离TTX，在中性条件下可逆结合。TTX结合物质结合STX而不是TTX，但不结合弓形虫毒素。观察TTX结合物质对TTX或STX致死活性的中和作用。在小鼠体内，TTX或STX的致死活性显著降低。日本鳗是携带TTX的动物之一。标本从岩手县三里库镇不同垂直水平的几个地点采集。用小鼠试验法对标本进行毒性测定。在特定地点捕获的样本中，毒性存在很大的个体差异。毒性的局部差异也很大。在高海拔地区采集的样品有毒性高于低海拔地区的趋势。从海滨附近的稻田收集的蝾螈，在从稻田运送到靠近山顶的沼泽100天后，其毒性增加。

High molecular weight substances (TTX-binding substances) which had ability to bind tetrodotoxin (TTX) were proved to be contained in the blood plasma of puffer fishes. Most of TTX in the plasma existed in a state of binding with the subsances. The TTX-binding substances had ability to bind not only TTX but also saxitoxin (STX). Small amount of STX bound with the substances existed naturally in the plasma. All the plasma of puffer fishes examined showed TTX-binding ability. In them the plasma of finepatterned puffer, Takifugu poecilonotus, showed the strongest activity, its one mililiter plasma could bind 23 mouse units of TTX.The TTX-binding substances unbound TTX under acidic condition and bound under neutral condition reversibly. The TTX-binding substances bound STX rather than TTX but did not bind goniotoxins. The TTX-binding substances were examined for neutralizing effects against the lethal activity of TTX or STX.When the mixture of the TTX-binding substances and TTX or STX was injected i.p. into mice, the lethal activity of TTX or STX was significantly reduced.Japanese newt is one of TTX-bearing animals. Specimens were collected from several spots at different vertical levels in Sanriku town, Iwate prefecture. The specimens were assayd for toxicity by mouse assay. A wide individual variation of toxicity was recognized among the specimens caught from a given spot. The local variation in toxicity was also large. There was a tendency that the toxicity was higher in specimens collected at high elevation than at low elevation. Toxicity of the newts collected from rice fields near seashore was increased 100 days after transportation them from the rice fields to a marsh near the top of a mountain.