Wastewater‐derived antagonistic activities of G protein‐coupled receptor‐acting pharmaceuticals in river water

Abstract

Pharmaceuticals are widely detected in aquatic environments, and their potential risks to aquatic species are of concern because they are designed to be biologically active. Here, we used an in vitro assay, called the transforming growth factor α shedding assay, to measure the biological activities of G protein-coupled receptor (GPCR)-acting pharmaceuticals present in river water and effluents from municipal wastewater treatment plants (WWTPs) in Japan from 2014 to 2016. Antagonistic activities against angiotensin (AT1), dopamine (D2), adrenergic (β1), acetylcholine (M1) and histamine (H1) receptors were detected in river water, and were stronger downstream than upstream owing to effluent from WWTPs along the river. Ozonation at one WWTP reduced these activities. Concentrations of sulpiride (D2 antagonist) could explain 73% of antagonistic activities against the D2 receptor; those of metoprolol, atenolol and propranolol (β1 antagonists) could explain 16% of activities against the β1 receptor; and those of pirenzepine (M1 antagonist) could explain 15% of activities against the M1 receptor. Therefore, other receptor antagonists also occur. GPCR-acting pharmaceuticals should be given more attention in environmental monitoring and toxicity testing.

Bioanalytical Tools in Water Quality Assessment

“…Recent studies have applied a TGFα-shedding assay to assess the biological activity of pharmaceuticals that bind to G protein-coupled receptors (Zhang et al, 2018a;Ihara et al, 2020). SPE-enriched wastewater from Japan and the UK were applied, with most samples found to be angiotensin (AT1), dopamine (D2), adrenergic (β1), acetylcholine (M1) and histamine (H1) receptor antagonists (Zhang et al, 2018a).…”