Cyclic imine toxins exhibit fast acting neurotoxicity and lethality by respiratory arrest in mice explained by their potent antagonistic activity against muscular nicotinic acetylcholine receptors. We performed a survey of gymnodimine-A, 13-desmethyl spirolide-C, 13,19-didesmethyl spirolide-C, 20-methyl spirolide-G, pinnatoxin-A, pinnatoxin-G, portimine-A and 28-O-palmitoyl ester of pinnatoxin-G in 36 shellfish samples collected in coastal areas of 8 European countries using a microplate receptor binding assay and UPLC-MS/MS for toxin identification and quantification. The major toxins found in these samples were pinnatoxin-G, 20-methyl spirolide-G, 13-desmethyl spirolide-C, gymnodimine-A and portimine-A. Traces of 13,19-didesmethyl spirolide-C, pinnatoxin-A and 28-O-palmitoyl ester of pinnatoxin-G were also detected. The rapid death of mice was correlated with higher pinnatoxin-G concentrations in mussel digestive gland extracts injected intraperitoneally. Our survey included nontoxic control samples that were found to contain moderate to trace amounts of several cyclic imine toxins. Shellfish may bioaccumulate not only cyclic imine toxins but also a large number of acyl derivatives as a product of metabolic transformation of these neurotoxins. This is the first report in which portimine-A and 28-O-palmitoyl ester of pinnatoxin-G were detected in shellfish extracts from digestive glands of mussels collected in Ingril lagoon. The bioaccumulation of portimine-A is particularly of concern because it is cytotoxic and is able to induce apotosis. The mode of action of 28-O-palmitoyl ester of pinnatoxin-G was studied by receptor binding-assay and by two-electrode voltage clamp electrophysiology. The antagonistic behavior of the acylated pinnatoxin-G towards nicotinic acetylcholine receptor of muscle type is shown here for the first time. Since cyclic imine toxins are not regulated further monitoring of these emerging toxins is needed to improve evidence gathering of their occurrence in shellfish commercialized for human consumption in Europe given their potent antagonism against muscle and neuronal nicotinic acetylcholine receptors.

环状亚胺毒素在小鼠呼吸停止时表现出快速作用的神经毒性和致死性，原因是它们对肌肉烟碱乙酰胆碱受体具有强效拮抗活性。我们对裸线二甲胺-A、13-去甲基螺内酯-C、13,19-二去甲基螺内酯-C、20-甲基螺内酯-G、羽扇豆毒素-A、羽藻毒素-G、波丁胺-A和28- O-棕榈酸酯进行了调查使用微孔板受体结合测定和 UPLC-MS/MS 对在 8 个欧洲国家的沿海地区收集的 36 个贝类样品中的 pinnatoxin-G 进行毒素鉴定和定量分析。在这些样品中发现的主要毒素是羽衣甘蓝毒素-G、20-甲基螺内酯-G、13-去甲基螺内酯-C、赤霉素-A 和波丁胺-A。痕量 13,19-二去甲基螺内酯-C、pinnatoxin-A 和 28- O还检测到pinnatoxin-G的-棕榈酸酯。小鼠的快速死亡与腹膜内注射的贻贝消化腺提取物中较高的 pinnatoxin-G 浓度相关。我们的调查包括无毒对照样品，这些样品被发现含有中等至痕量的几种环亚胺毒素。贝类不仅可以生物积累环状亚胺毒素，还可以生物积累大量酰基衍生物，作为这些神经毒素代谢转化的产物。这是第一次在 Ingril 泻湖收集的贻贝消化腺的贝类提取物中检测到Portimine-A 和 28- O -pinnatoxin- G 棕榈酰酯的报告。Portimine-A 的生物蓄积性尤其值得关注，因为它具有细胞毒性并且能够诱导细胞凋亡。28-的作用方式通过受体结合测定和双电极电压钳电生理学研究了羽衣毒素-G的O-棕榈酸酯。此处首次展示了酰化羽衣毒素-G 对肌肉型烟碱型乙酰胆碱受体的拮抗行为。由于环状亚胺毒素不受监管，因此需要对这些新出现的毒素进行进一步监测，以改进在欧洲用于人类消费的贝类中它们发生的证据收集，因为它们对肌肉和神经元烟碱乙酰胆碱受体具有强大的拮抗作用。