title: Detection of physiological activities of G protein-coupled receptor-acting pharmaceuticals in wastewater.
abstract: Although pharmaceuticals are generally found at very low levels in aquatic environments, concern about their potential risks to humans and aquatic species has been raised because they are designed to be biologically active. To resolve this concern, we must know whether the biological activity of pharmaceuticals can be detected in waters. Nearly half of all marketed pharmaceuticals act by binding to the G protein-coupled receptors (GPCRs). In this study, we measured the physiological activity of pharmaceuticals in wastewater. We applied the in vitro transforming growth factor-α (TGFα) shedding assay, which accurately and sensitively detect GPCR activation, to investigate the agonistic/antagonistic activities of wastewater extracts against receptors for angiotensin (AT1), dopamine (D2, D4), adrenergic family members (α1B, α2A, β1, β3), acetylcholine (M1, M3), cannabinoid (CB1), vasopressin (V1A, V2), histamine (H1, H2, H3), 5-hydroxytryptamine (5-HT1A, 5-HT2C), prostanoid (EP3), and leukotriene (BLT1). As a result, antagonistic activity against AT1, D2, α1B, β1, M1, M3, H1, and V2 receptors was detected at up to several μg/L for the first time. Agonistic activity against α2A receptor was also detected. The TGFα shedding assay is useful for measuring the physiological activity of GPCR-acting pharmaceuticals in the aquatic environment.
authors.affiliation: Research Center for Environmental Quality Management, Graduate School of Engineering, Kyoto University , Otsu, Shiga 520-0811, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Ihara
authors.forename: Asuka
authors.initials: A
authors.lastname: Inoue
authors.forename: Seiya
authors.initials: S
authors.lastname: Hanamoto
authors.forename: Han
authors.initials: H
authors.lastname: Zhang
authors.forename: Junken
authors.initials: J
authors.lastname: Aoki
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Tanaka
mesh_terms: D006801:Humans; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction; D062065:Wastewater; D014874:Water Pollutants, Chemical / Q000378:metabolism*
chemical_list: D004364:Pharmaceutical Preparations; D043562:Receptors, G-Protein-Coupled; D062065:Wastewater; D014874:Water Pollutants, Chemical