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Stop the crop: Insights into the insecticidal mode of action of cinnamodial against mosquitoes
Pesticide Biochemistry and Physiology ( IF 4.2 ) Pub Date : 2021-01-01 , DOI: 10.1016/j.pestbp.2020.104743 Megha Kalsi 1 , Anton Walter 1 , Beenhwa Lee 1 , Andrew DeLaat 1 , Renata Rusconi Trigueros 1 , Katharina Happel 1 , Rose Sepesy 1 , Bao Nguyen 1 , Preston K Manwill 2 , Liva Harinantenaina Rakotondraibe 2 , Peter M Piermarini 3
Pesticide Biochemistry and Physiology ( IF 4.2 ) Pub Date : 2021-01-01 , DOI: 10.1016/j.pestbp.2020.104743 Megha Kalsi 1 , Anton Walter 1 , Beenhwa Lee 1 , Andrew DeLaat 1 , Renata Rusconi Trigueros 1 , Katharina Happel 1 , Rose Sepesy 1 , Bao Nguyen 1 , Preston K Manwill 2 , Liva Harinantenaina Rakotondraibe 2 , Peter M Piermarini 3
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Cinnamodial (CDIAL) is a drimane sesquiterpene dialdehyde found in the bark of Malagasy medicinal plants (Cinnamosma species; family Canellaceae). We previously demonstrated that CDIAL was insecticidal, antifeedant, and repellent against Aedes aegypti mosquitoes. The goal of the present study was to generate insights into the insecticidal mode of action for CDIAL, which is presently unknown. We evaluated the effects of CDIAL on the contractility of the ventral diverticulum (crop) isolated from adult female Ae. aegypti. The crop is a food storage organ surrounded by visceral muscle that spontaneously contracts in vitro. We found that CDIAL completely inhibited spontaneous contractions of the crop as well as those stimulated by the agonist 5-hydroxytryptamine. Several derivatives of CDIAL with known insecticidal activity also inhibited crop contractions. Morphometric analyses of crops suggested that CDIAL induced a tetanic paralysis that was dependent on extracellular Ca2+ and inhibited by Gd3+, a non-specific blocker of plasma membrane Ca2+ channels. Screening of numerous pharmacological agents revealed that a Ca2+ ionophore (A23187) was the only compound other than CDIAL to completely inhibit crop contractions via a tetanic paralysis. Taken together, our results suggest that CDIAL induces a tetanic paralysis of the crop by elevating intracellular Ca2+ through the activation of plasma membrane Ca2+ channels, which may explain the insecticidal effects of CDIAL against mosquitoes. Our pharmacological screening experiments also revealed the presence of two regulatory pathways in mosquito crop contractility not previously described: an inhibitory glutamatergic pathway and a stimulatory octopaminergic pathway. The latter pathway was also completely inhibited by CDIAL.
中文翻译：
停止作物：深入了解肉桂对蚊子的杀虫作用方式
肉桂 (CDIAL) 是一种 drimane 倍半萜二醛，存在于马达加斯加药用植物（Cinnamosma 种；Canellaceae 科）的树皮中。我们之前已经证明 CDIAL 对埃及伊蚊具有杀虫、拒食和驱虫作用。本研究的目的是深入了解 CDIAL 的杀虫作用模式，目前尚不清楚。我们评估了 CDIAL 对从成年雌性 Ae 分离的腹侧憩室（作物）收缩力的影响。埃及人。作物是一种食物储存器官，被内脏肌肉包围，在体外会自发收缩。我们发现 CDIAL 完全抑制了作物的自发收缩以及由激动剂 5-羟色胺刺激的收缩。几种具有已知杀虫活性的 CDIAL 衍生物也抑制了作物收缩。作物的形态测量分析表明，CDIAL 诱导强直性麻痹，该麻痹依赖于细胞外 Ca2+ 并被 Gd3+（一种质膜 Ca2+ 通道的非特异性阻滞剂）抑制。对众多药理学试剂的筛选表明，Ca2+ 离子载体 (A23187) 是除 CDIAL 之外唯一通过强直性麻痹完全抑制作物收缩的化合物。总之，我们的结果表明 CDIAL 通过激活质膜 Ca2+ 通道提高细胞内 Ca2+ 诱导作物的强直性麻痹，这可以解释 CDIAL 对蚊子的杀虫作用。我们的药理学筛选实验还揭示了蚊子作物收缩性中存在两种以前未描述的调节途径：抑制性谷氨酸能途径和刺激性章鱼胺能途径。CDIAL 也完全抑制了后一种途径。
更新日期：2021-01-01
中文翻译：
停止作物：深入了解肉桂对蚊子的杀虫作用方式
肉桂 (CDIAL) 是一种 drimane 倍半萜二醛，存在于马达加斯加药用植物（Cinnamosma 种；Canellaceae 科）的树皮中。我们之前已经证明 CDIAL 对埃及伊蚊具有杀虫、拒食和驱虫作用。本研究的目的是深入了解 CDIAL 的杀虫作用模式，目前尚不清楚。我们评估了 CDIAL 对从成年雌性 Ae 分离的腹侧憩室（作物）收缩力的影响。埃及人。作物是一种食物储存器官，被内脏肌肉包围，在体外会自发收缩。我们发现 CDIAL 完全抑制了作物的自发收缩以及由激动剂 5-羟色胺刺激的收缩。几种具有已知杀虫活性的 CDIAL 衍生物也抑制了作物收缩。作物的形态测量分析表明，CDIAL 诱导强直性麻痹，该麻痹依赖于细胞外 Ca2+ 并被 Gd3+（一种质膜 Ca2+ 通道的非特异性阻滞剂）抑制。对众多药理学试剂的筛选表明，Ca2+ 离子载体 (A23187) 是除 CDIAL 之外唯一通过强直性麻痹完全抑制作物收缩的化合物。总之，我们的结果表明 CDIAL 通过激活质膜 Ca2+ 通道提高细胞内 Ca2+ 诱导作物的强直性麻痹，这可以解释 CDIAL 对蚊子的杀虫作用。我们的药理学筛选实验还揭示了蚊子作物收缩性中存在两种以前未描述的调节途径：抑制性谷氨酸能途径和刺激性章鱼胺能途径。CDIAL 也完全抑制了后一种途径。
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