近日，中国科学院昆明动物研究所研究员赖仞、中国科学院上海药物研究所研究员林东海、湖南师范大学教授梁宋平等率领的研究团队，通过合作，从华西雨蛙的皮肤分泌液中发现了基因编码的神经毒，被命名为anntoxin。该毒素含有60个氨基酸残基、拥有2个分子内二硫键、通过阻断河豚毒素敏感的钠通道发挥神经毒活性。该毒素主要分布于华西雨蛙皮肤中，其含量高达25微克／克皮肤湿组织。它对昆虫、爬行类、鸟类和哺乳类动物具有强的致死毒性。Anntoxin与眼镜蛇毒来源的神经毒有显著的结构同源性，也表现部分生物活性的相似性。这些结构和功能相似性暗示了动物毒素的一种可能的进化联系。以前也有关于两栖动物南美箭毒蛙的生物碱毒素的报道，但其不是由基因编码的，而是来源于其食物（如昆虫），是不可遗传的，而目前发现的两栖动物神经毒素为基因编码产物。

在鱼类、爬行类、哺乳类动物以及无脊椎动物中早已发现了大量的基因编码的神经毒，却一直没有从两栖动物中发现基因编码的神经毒。

该研究成果已正式发表于国际著名学术刊物J Biol Chem. 2009，284(33):22079-86上，题目为The First Gene-encoded Amphibian Neurotoxin，并被美国生物化学与分子生物学联合会作为亮点工作重点报道。

推荐原始出处：

J. Biol. Chem., Vol. 284, Issue 33, 22079-22086, August 14, 2009

The First Gene-encoded Amphibian Neurotoxin*

Dewen You1, Jing Hong?1, Mingqiang Rong||1, Haining Yu**, Songping Liang||, Yufang Ma, Hailong Yang, Jing Wu, Donghai Lin?2, and Ren Lai3

From the From the Biotoxin Units of Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, , the ?Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, , the ||The Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha 410081, , the **College of Life Sciences, Hebei Normal University, Shijiazhuang 050016, Hebei, and , the Graduate School of the Chinese Academy of Sciences, Beijing 100009, China

Many gene-encoded neurotoxins with various functions have been discovered in fish, reptiles, and mammals. A novel 60-residue neurotoxin peptide (anntoxin) that inhibited tetrodotoxin-sensitive (TTX-S) voltage-gated sodium channel (VGSC) was purified and characterized from the skin secretions of the tree frog Hyla annectans (Jerdon). This is the first gene-encoded neurotoxin found in amphibians. The IC50 of anntoxin for the TTX-S channel was about 3.4 μM. Anntoxin shares sequence homology with Kunitz-type toxins but contains only two of three highly conserved cysteine bridges, which are typically found in these small, basic neurotoxin modules, i.e. snake dendrotoxins. Anntoxin showed an inhibitory ability against trypsin with an inhibitory constant (Ki) of 0.025 μM. Anntoxin was distributed in skin, brain, stomach, and liver with a concentration of 25, 7, 3, and 2 μg/g wet tissue, respectively. H. annectans lives on trees or other plants for its entire life cycle, and its skin contains the largest amount of anntoxin, which possibly helps defend against various aggressors or predators. A low dose of anntoxin was found to induce lethal toxicity for several potential predators, including the insect, snake, bird, and mouse. The tissue distribution and functional properties of the current toxin may provide insights into the ecological adaptation of tree-living amphibians.