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

在河豚鱼的血浆中发现了能够结合河豚毒素（TTX）的高分子量物质（TTX结合物质）。血浆中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，还能结合石蜡毒素（STX）。少量STX与这些物质结合，自然存在于血浆中。所有检测的河豚血浆均显示ttx结合能力。其中，细纹河豚（Takifugu poecilonotus）的血浆活性最强，其1毫升血浆可结合23个小鼠单位的TTX。TTX结合物质在酸性条件下与TTX分离，在中性条件下与TTX可逆结合。TTX结合物质与STX结合而不是TTX，但不与性腺毒素结合。检测了TTX结合物质对TTX或STX致死活性的中和作用。将TTX结合物质与TTX或STX的混合物灌胃小鼠后，TTX或STX的致死活性明显降低。日本蝾螈是一种携带ttx的动物。在岩手县三陆镇不同垂直高度的几个地点采集了标本。小鼠毒性试验。在一个给定地点捕获的标本中，毒性的个体差异很大。毒性的局部差异也很大。在高海拔地区采集的标本的毒性有高于低海拔地区的趋势。从靠近海岸的稻田中采集的蝾螈，从稻田转移到靠近山顶的沼泽中100天后，其毒性有所增加。

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.