Unit of Mode of Toxin Action (MATx), Laboratory of Pharmacology, Butantan Institute, São Paulo, Brazil; Department of Pharmacology, Federal University of São Paulo (UNIFESP), São Paulo, Brazil.
Department of Pharmacology, Federal University of São Paulo (UNIFESP), São Paulo, Brazil.
Auton Neurosci. 2020 Sep;227:102676. doi: 10.1016/j.autneu.2020.102676. Epub 2020 May 19.
Scorpion envenomation is a public health problem in tropical and subtropical areas. In Brazil, Tityus serrulatus is the biggest cause of accidents with venomous animals. Tityus serrulatus venom causes symptoms related to a great activation of the autonomic system attributed to a massive release of sympathetic and parasympathetic mediators. This effect is attributed to the presence of toxins acting in Na and K ion channels, leading to an increase in cell excitability. Although gastrointestinal symptoms, like diarrhoea and sialorrhea, is observed in moderate to severe cases, little attention is given in clinical reports. Gastrointestinal motility is controlled by the enteric nervous system which is composed of a wide variety of interconnected neurons that are influenced by the sympathetic and parasympathetic nervous systems. Thus, this work aimed to characterize the effects of Tityus serrulatus venom on sympathetic and parasympathetic neurotransmission of rat jejunum, as well as to investigate possibles effects on other neurons of the enteric nervous system. To this, we verify the effects of Tityus serrulatus venom on the contractility of isolated rat jejunum through organ-bath experiments. We observed that venom can induce both contraction and relaxation. The contraction was partially inhibited by atropine (1 μM) and by suramin (0.1 mM) through tetrodotoxin-resistant and sensitive mechanisms. The relaxation was completely inhibited by 3 μM propranolol and partially inhibited by 1 μM phentolamine. Suramin induced a slowing of relaxation curve. Tetrodotoxin completely inhibits the relaxation induced by Tityus serrulatus venom, but the contraction curves were only partially reduced in their initial portion. The final part of the curve was largely enhanced by Tetrodotoxin. Atropine blocks almost completely the contraction curve in the presence of Tetrodotoxin. These results indicate that Tityus serrulatus venom induces the release of both excitatory (predominantly acetylcholine) and inhibitory (mainly noradrenaline) neurotransmitters. The effects of Tityus serrulatus venom on organ contractility was quite complex and seem to derive from a diffuse and nonspecific release of mediators from autonomic and enteric nervous systems. Further investigation of venom action and its isolated toxins can reveal important aspects to deepen our knowledge about the enteric nervous system transmission and the interaction between excitatory and inhibitory mediators as well as the physiological role of Na and K ion channels in gut motility.
蝎子螫伤是热带和亚热带地区的一个公共卫生问题。在巴西，Tityus serrulatus 是导致动物毒液伤害的最大原因。Tityus serrulatus 毒液引起的症状与自主神经系统的巨大激活有关，这归因于大量释放交感神经和副交感神经递质。这种效应归因于存在作用于 Na 和 K 离子通道的毒素，导致细胞兴奋性增加。尽管在中度至重度病例中观察到胃肠道症状，如腹泻和流涎，但在临床报告中很少关注。胃肠道运动由肠神经系统控制，肠神经系统由广泛相互连接的神经元组成，受交感神经和副交感神经系统的影响。因此，这项工作旨在表征 Tityus serrulatus 毒液对大鼠空肠交感和副交感神经递质传递的影响，并研究其对肠神经系统中其他神经元的可能影响。为此，我们通过器官浴实验验证了 Tityus serrulatus 毒液对分离大鼠空肠收缩性的影响。我们观察到毒液可以诱导收缩和松弛。毒蕈碱（1 μM）和苏拉明（0.1 mM）通过河豚毒素抗性和敏感机制部分抑制收缩。3 μM 心得安完全抑制松弛，1 μM 酚妥拉明部分抑制松弛。苏拉明引起松弛曲线减慢。河豚毒素完全抑制 Tityus serrulatus 毒液诱导的松弛，但在其初始部分部分减少收缩曲线。曲线的最后一部分在很大程度上被河豚毒素增强。毒蕈碱在存在河豚毒素的情况下几乎完全阻断收缩曲线。这些结果表明，Tityus serrulatus 毒液诱导释放兴奋性（主要是乙酰胆碱）和抑制性（主要是去甲肾上腺素）神经递质。Tityus serrulatus 毒液对器官收缩性的影响非常复杂，似乎源于自主神经和肠神经系统中介质的弥散和非特异性释放。对毒液作用及其分离毒素的进一步研究可以揭示重要方面，以加深我们对肠神经系统传递以及兴奋性和抑制性介质相互作用的了解，以及 Na 和 K 离子通道在肠道运动中的生理作用。
