Biological Activity-Based Prioritization of Pharmaceuticals in Wastewater for Environmental Monitoring: G Protein-Coupled Receptor Inhibitors
Biological Activity-Based Prioritization of Pharmaceuticals in Wastewater for Environmental Monitoring: G Protein-Coupled Receptor Inhibitors
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用于环境监测的废水中基于生物活性的药物优先排序：G 蛋白偶联受体抑制剂
DOI：
10.1021/acs.est.9b05768
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发表时间：
2020
影响因子：
11.4
通讯作者：
Ihara Masaru
中科院分区：
文献类型：
--
作者：
Zhang Han;Ihara Mariko O.;Nakada Norihide;Tanaka Hiroaki;Ihara Masaru
药品因其生物活性而引起人们对水生物种的关注。据估计，近 40% 的市售药物以 G 蛋白偶联受体 (GPCR) 为靶点。使用体外转化生长因子-α (TGFα) 脱落测定，我们之前检测到废水中高达 μg 拮抗剂当量/L 的 GPCR 作用药物对血管紧张素 (AT1)、多巴胺 (D2)、乙酰胆碱 (M1)、肾上腺素能家族成员 (β1) 和组胺 (H1) 受体的拮抗活性 在英国和日本。然而，哪些药物导致废水中的生物活性仍不清楚。在这里，我们使用（1）根据处方计算的 GPCR 作用药物（特别是拮抗剂）的消耗量，（2）它们的尿液排泄量，以及（3）通过 TGFα 脱落测定测量的它们的效力，以优先考虑它们在英国和日本的废水中进行分析。我们计算了英国和日本进水中 48 种 GPCR 作用药物的预测活性，并确定了废水中针对每种 GPCR 的拮抗活性的主要药物。本研究中测试的药物混合物被证实具有相加作用。消耗量和效力的结合有助于确定药物的优先顺序以进行环境监测和毒性测试。
Pharmaceuticals raise concerns for aquatic species owing to their biological activities. It is estimated that nearly 40% of marketed pharmaceuticals target G protein-coupled receptors (GPCRs). Using an in vitro transforming growth factor-α (TGFα) shedding assay, we previously detected antagonistic activities of GPCR-acting pharmaceuticals against angiotensin (AT1), dopamine (D2), acetylcholine (M1), adrenergic family members (β1), and histamine (H1) receptors at up to μg-antagonist-equivalent quantities/L in wastewater in England and Japan. However, which pharmaceuticals were responsible for biological activities in wastewater remained unclear. Here, we used (1) the consumption of GPCR-acting pharmaceuticals, particularly antagonists, as calculated from prescriptions, (2) their urinary excretion, and (3) their potency measured by the TGFα shedding assay to prioritize them for analysis in wastewater in England and Japan. We calculated predicted activities of 48 GPCR-acting pharmaceuticals in influents in England and Japan and identified which were mainly responsible for antagonistic activities in wastewater against each GPCR. Mixtures of pharmaceuticals tested in this study were confirmed to behave additively. The combination of consumption and potency is useful in prioritizing pharmaceuticals for environmental monitoring and toxicity testing.