RT Journal
A1 Kajiya, Kentaro
A1 Inaki, Koichiro
A1 Tanaka, Motonari
A1 Haga, Tatsuya
A1 Kataoka, Hiroshi
A1 Touhara, Kazushige
T1 Molecular Bases of Odor Discrimination: Reconstitution of Olfactory Receptors that Recognize Overlapping Sets of Odorants
JF The Journal of Neuroscience 
JO The Journal of Neuroscience 
YR 2001 
FD August 15 
VO 21 
IS 16 
SP 6018 
OP 6025 
DO 10.1523/JNEUROSCI.21-16-06018.2001 
UL http://www.jneurosci.org/content/21/16/6018.abstract 
AB The vertebrate olfactory system discriminates a wide variety of odorants by relaying coded information from olfactory sensory neurons in the olfactory epithelium to olfactory cortical areas of the brain. Recent studies have shown that the first step in odor discrimination is mediated by ∼1000 distinct olfactory receptors, which comprise the largest family of G-protein-coupled receptors. In the present study, we used Ca2+ imaging and single-cell reverse transcription-PCR techniques to identify mouse olfactory neurons responding to an odorant and subsequently to clone a receptor gene from the responsive cell. The functionally cloned receptors were expressed in heterologous systems, demonstrating that structurally related olfactory receptors recognized overlapping sets of odorants with distinct affinities and specificities. Our results provide direct evidence for the existence of a receptor code in which the identities of different odorants are specified by distinct combinations of odorant receptors that possess unique molecular receptive ranges. We further demonstrate that the receptor code for an odorant changes with odorant concentration. Finally, we show that odorant receptors in human embryonic kidney 293 cells couple to stimulatory G-proteins such as Gαolf, resulting in odorant-dependent increases in cAMP. Odor discrimination is thus determined by differences in the receptive ranges of the odorant receptors that together encode specific odorant molecules.