Antagonistic interactions between odorants alter human odor perception

Abstract

The olfactory system detects a vast number of odorants using hundreds of olfactory receptors (ORs), the largest group of the G protein-coupled receptor (GPCR) superfamily. Each OR is activated by specific odorous ligands. Like other GPCRs, activation of ORs may be blocked through antagonism. Recent reports highlight widespread antagonisms in odor mixtures influencing olfactory neuron activities. However, it is unclear if and how these antagonisms influence perception of odor mixtures. Here we show that odorant antagonisms at the receptor level alter odor perception. Using a large-scale heterologous expression, we first identified a set of human ORs that are activated by methanethiol and hydrogen sulfide, two extremely potent volatile sulfur malodors. We then screened odorants that block activation of these ORs and identified a set of antagonists, including β-ionone. Finally, human sensory evaluation revealed that odor intensity and unpleasantness of methanethiol were decreased by β-ionone. Odor intensity of β-ionone itself is not correlated with the degree of suppression of malodor sensation. Suppression was also not observed when methanethiol and β-ionone were simultaneously introduced to different nostrils. Together, our data supports the model that odor sensation is altered through antagonistic interactions at the level of the ORs.