Antagonistic interactions between odorants alter human odor perception

The olfactory system uses hundreds of odorant receptors (ORs), the largest group of the G-protein-coupled receptor (GPCR) superfamily, to detect a vast array of odorants. Each OR is activated by specific odorous ligands, and like other GPCRs, antagonism can block activation of ORs. Recent studies suggest that odorant antagonisms in mixtures influence olfactory neuron activities, but it is unclear how this affects perception of odor mixtures. In this study, we identified a set of human ORs activated by methanethiol and hydrogen sulfide, two potent volatile sulfur malodors, through large-scale heterologous expression. Screening odorants that block OR activation in heterologous cells identified a set of antagonists, including β-ionone. Sensory evaluation in humans revealed that β-ionone reduced the odor intensity and unpleasantness of methanethiol. Additionally, suppression was not observed when methanethiol and β-ionone were introduced simultaneously to different nostrils. Our study supports the hypothesis that odor sensation is altered through antagonistic interactions at the OR level. [Display omitted] •β-ionone antagonizes activation of odorant receptors responding to sulfur malodors•β-ionone suppresses malodor intensity and unpleasantness in sensory evaluations•No suppression observed when malodor and β-ionone introduced to different nostrils•Odor sensation is likely to be altered via OR-level antagonistic interactions Fukutani et al. identified β-ionone as an antagonist of odorant receptors responding to potent sulfur malodors using heterologous expression. Human sensory evaluations confirmed β-ionone effectively reduced malodor intensity and unpleasantness, highlighting the importance of antagonistic interactions at the odorant receptor level in odor sensation.