Toxicology Centre, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
Laboratoire de Biologie des Ligneux et des Grandes Cultures (LBLGC), USC INRAE 1328, Université d'Orléans, Orléans, France.
Aquat Toxicol. 2021 Jan;230:105701. doi: 10.1016/j.aquatox.2020.105701. Epub 2020 Nov 23.
Neonicotinoids are neuroactive insecticides commonly detected in freshwater ecosystems. Recent studies have indicated that these compounds are markedly toxic to Chironomidae, a widespread family of ecologically important aquatic insects. However, despite their sensitivity, the pharmacological mechanisms driving neonicotinoid toxicity have yet to be characterized in these insect species. Here, we used a combination of saturation and competition binding studies to characterize neonicotinoid binding properties to nicotinic acetylcholine receptors (nAChR) in two different Chironomidae (Chironomus riparius and Chironomus dilutus) at two different life stages (larval and adult). Using radiolabeled imidacloprid ([H]-IMI), we characterized and compared receptor density (B), imidacloprid binding affinity (K), and receptor binding affinity (K) to three different neonicotinoid competitors (imidacloprid, clothianidin, and thiamethoxam). We then compared receptor density and binding affinity parameters derived for Chironomidae to data previously generated for other dipterans and agricultural pests. We found that there were limited differences in neonicotinoid binding between C. riparius and C. dilutus, with both organisms demonstrating high affinities for imidacloprid (K = 0.22-0.87 nM) and high receptor densities (B = 0.92-6.53 pmol/mg). However, there were significant differences between life-stages, with larvae expressing higher densities of nicotinic acetylcholine receptors and higher imidacloprid affinities than adults. Moreover, there were compound-specific differences in receptor affinity, with larval stages displaying relative affinities (K) that generally correlated with acute neonicotinoid toxicity (e.g. clothianidin ≥ imidacloprid >>> thiamethoxam). Finally, compared to other dipterans and agricultural pests, Chironomidae display very high densities of high affinity nicotinic acetylcholine receptors, which likely contribute to their sensitivity. Results indicated that receptor-level differences in neonicotinoid binding may be responsible for ecotoxicological differences amongst distinct insect species, and they likely play a role in life stage-, and compound-level toxicity differences previously observed for Chironomidae. Overall, this study highlights the value of understanding the toxicological mechanisms of action of neonicotinoids in sensitive, non-target aquatic insects, to better predict adverse effects associated with unintentional neonicotinoid exposure.
新烟碱类杀虫剂是常见的淡水生态系统中的神经活性杀虫剂。最近的研究表明，这些化合物对摇蚊科，一种广泛存在的生态重要水生昆虫，具有显著的毒性。然而，尽管它们具有敏感性，但新烟碱类化合物毒性的药理学机制尚未在这些昆虫物种中得到描述。在这里，我们使用饱和和竞争结合研究的组合，来描述两种不同摇蚊科（Chironomus riparius 和 Chironomus dilutus）在两个不同生命阶段（幼虫和成虫）的新烟碱类化合物与烟碱型乙酰胆碱受体（nAChR）的结合特性。使用放射性标记的吡虫啉（[H]-IMI），我们对受体密度（B）、吡虫啉结合亲和力（K）和受体结合亲和力（K）进行了表征和比较，这些参数针对三种不同的新烟碱类竞争物（吡虫啉、噻虫啉和噻虫嗪）。然后，我们将从摇蚊科获得的受体密度和结合亲和力参数与先前为其他双翅目昆虫和农业害虫生成的数据进行了比较。我们发现，C. riparius 和 C. dilutus 之间的新烟碱类化合物结合差异有限，两种生物对吡虫啉都表现出高亲和力（K = 0.22-0.87 nM）和高受体密度（B = 0.92-6.53 pmol/mg）。然而，在生命阶段之间存在显著差异，幼虫表达的烟碱型乙酰胆碱受体密度更高，对吡虫啉的亲和力也更高。此外，在受体亲和力方面存在化合物特异性差异，幼虫阶段表现出的相对亲和力（K）通常与急性新烟碱类毒性相关（例如，噻虫啉≥吡虫啉＞＞噻虫嗪）。最后，与其他双翅目昆虫和农业害虫相比，摇蚊科显示出非常高的高亲和力烟碱型乙酰胆碱受体密度，这可能是它们对新烟碱类敏感的原因。结果表明，新烟碱类化合物结合的受体水平差异可能是不同昆虫物种之间生态毒理学差异的原因，并且可能在先前观察到的摇蚊科的生命阶段和化合物水平毒性差异中发挥作用。总的来说，这项研究强调了在敏感的非靶标水生昆虫中了解新烟碱类化合物作用的毒理学机制的价值，以便更好地预测与意外接触新烟碱类相关的不良影响。
