Plastic chemicals disrupt molecular circadian rhythms via adenosine 1 receptor in vitro

The adenosine 1 receptor (A₁R) is a G protein-coupled receptor that transduces signals to regulate sleep-wake cycles and circadian rhythms. Plastic products contain thousands of chemicals, known to disrupt physiological function. Recent research has demonstrated that some of these chemicals are also A₁R agonists, however, the extent to which such activation propagates downstream and results in cellular alterations remains unknown. Thus, we investigate whether chemicals extracted from polyurethane (PUR) and polyvinyl chloride (PVC) plastics disrupt circadian rhythms via agonism of A₁R. We confirm that plastic chemicals in both plastics activate A₁R and inhibit intracellular cAMP in U2OS cells. Notably, this inhibition is comparable to that induced by the highly specific A₁R agonist 2'-MeCCPA. To assess circadian disruption, we quantify temporal expression patterns of the clock genes PER2 and CRY2 at 4-h intervals over 48 h. Here, exposure to plastic chemicals shifts the phase in the oscillatory expression cycles of both clock genes by 9-17 min. Importantly, these effects are dose-dependent and reversible when A₁R is inhibited by a pharmacological antagonist. This demonstrates that plastic chemicals can disrupt circadian processes by interfering with A₁R signaling and suggests a novel mechanism by which these and other chemicals may contribute to non-communicable diseases.