Lys49 myotoxin from the Brazilian lancehead pit viper elicits pain through regulated ATP release

作者：Chuchu Zhang, Katalin F. Medzihradszky, Elda E. Sánchez, Allan I. Basbaum, David Julius · 发表于：Proceedings of the National Academy of Sciences · 年份：2017 · DOI：10.1073/pnas.1615484114 · 被引用次数：46 · 研究领域：Venomous Animal Envenomation and Studies、Pain Mechanisms and Treatments、Ion channel regulation and function

Significance Bites from venomous snakes can inflict substantial pain and inflammatory tissue damage. Snake phospholipase A2 (PLA2), and PLA2-like toxins that retain the PLA2 fold but lack enzymatic activity, are commonly found in snake venoms. In this study, we identify a PLA2-like toxin (BomoTx), from the Brazilian lancehead pit viper ( Bothrops moojeni ), that activates a subpopulation of somatosensory neurons that contribute to pain sensation. We show that BomoTx excites these neurons by stimulating the release of cellular ATP through a mechanism involving pannexin hemichannels. Consequent activation of purinergic receptors elicits acute pain, tissue inflammation, and pain hypersensitivity. Thus, we have elucidated the mechanism of action for a toxin from Bothrops snakes, which inflict a majority of bites in Latin America.