An odorant derivative as an antagonist for an olfactory receptor.
Different odorants are recognized by different combinations of G protein-coupled olfactory receptors, and thereby, odor identity is determined by a combinatorial receptor code for each odorant. We recently demonstrated that odorants appeared to compete for receptor sites to act as an agonist or an antagonist. Therefore, in natural circumstances where we always perceive a mixture of various odorants, olfactory receptor antagonism between odorants may result in a receptor code for the mixture that cannot be predicted from the codes for its individual components. Here we show that stored isoeugenol has an antagonistic effect on a mouse olfactory receptor, mOR-EG. However, freshly purified isoeugenol did not have an inhibitory effect. Instead, an isoeugenol derivative produced during storage turned out to be a potent competitive antagonist of mOR-EG. Structural analysis revealed that this derivative is an oxidatively dimerized isoeugenol that naturally occurs by oxidative reaction. The current study indicates that as odorants age, they decompose or react with other odorants, which in turn affects responsiveness of an olfactory receptor(s).
Oka
Yuki
Y
Department of Integrated Biosciences, The University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8562, Japan.
Nakamura
Akio
A
Watanabe
Hidenori
H
Touhara
Kazushige
K
D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D004355:Drug Stability; D004356:Drug Storage; D005054:Eugenol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D009812:Odorants; D009821:Oils / Q000494:pharmacology; D018034:Olfactory Receptor Neurons / Q000187:drug effects*; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors
D009821:Oils; D043562:Receptors, G-Protein-Coupled; D005054:Eugenol; C036643:isoeugenol; D002118:Calcium