Suppression of Odors by Odorant Receptor Antagonists

Abstract

The vertebrate olfactory system recognizes and discriminates between thousands of structurally diverse odorants. Detection of odorants in mammals is mediated by odorant receptors, which comprise the largest superfamily of G-protein coupled receptors (GPCRs). As with other GPCRs, OR ligands are able to serve as both agonists and antagonists. To understand the correlation of the function of odorant receptors and human olfaction, we examined effects of antagonists of human odorant receptors for odor intensity in sensory evaluation. Screening of odorant receptors for Hexanoic acid revealed that five ORs -OR2W1, OR10A6, OR51E1, OR51I2 and OR51L1- responded to Hexanoic acid dose-dependently, and also some antagonists that inhibited the response of Hexanoic acid-receptors were identified. Next, sensory evaluation was performed to examine whether antagonists of Hexanoic acid-receptors could decreased the Hexanoic acid-odor. As a result, it was found that antagonists weakened Hexanoic acid-odor, suggesting the link between the function of ORs at peripheral level and human olfaction at cognition level.