title: Supersensitive detection and discrimination of enantiomers by dorsal olfactory receptors: evidence for hierarchical odour coding.
abstract: Enantiomeric pairs of mirror-image molecular structures are difficult to resolve by instrumental analyses. The human olfactory system, however, discriminates (-)-wine lactone from its (+)-form rapidly within seconds. To gain insight into receptor coding of enantiomers, we compared behavioural detection and discrimination thresholds of wild-type mice with those of ΔD mice in which all dorsal olfactory receptors are genetically ablated. Surprisingly, wild-type mice displayed an exquisite "supersensitivity" to enantiomeric pairs of wine lactones and carvones. They were capable of supersensitive discrimination of enantiomers, consistent with their high detection sensitivity. In contrast, ΔD mice showed selective major loss of sensitivity to the (+)-enantiomers. The resulting 10(8)-fold differential sensitivity of ΔD mice to (-)- vs. (+)-wine lactone matched that observed in humans. This suggests that humans lack highly sensitive orthologous dorsal receptors for the (+)-enantiomer, similarly to ΔD mice. Moreover, ΔD mice showed >10(10)-fold reductions in enantiomer discrimination sensitivity compared to wild-type mice. ΔD mice detected one or both of the (-)- and (+)-enantiomers over a wide concentration range, but were unable to discriminate them. This "enantiomer odour discrimination paradox" indicates that the most sensitive dorsal receptors play a critical role in hierarchical odour coding for enantiomer identification.
authors.affiliation: Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology, Hyogo 661-0974, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Sato
authors.affiliation: Institute of Biomedical Science, Kansai Medical University, Osaka 573-1010, Japan.
authors.forename: Reiko
authors.initials: R
authors.lastname: Kobayakawa
authors.affiliation: Institute of Biomedical Science, Kansai Medical University, Osaka 573-1010, Japan.
authors.forename: Ko
authors.initials: K
authors.lastname: Kobayakawa
authors.affiliation: Takasago International Corporation, Kanagawa 254-0073, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Emura
authors.affiliation: Laboratory for Behavioral Genetics, Brain Science Institute, RIKEN, Saitama 351-0198, Japan.
authors.forename: Shigeyoshi
authors.initials: S
authors.lastname: Itohara
authors.affiliation: Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology, Hyogo 661-0974, Japan.
authors.forename: Miwako
authors.initials: M
authors.lastname: Kizumi
authors.affiliation: Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology, Hyogo 661-0974, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hamana
authors.affiliation: Research Institute of Frontier Medicine, Nara Medical University, Nara 634-8521, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Tsuboi
authors.affiliation: Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology, Hyogo 661-0974, Japan.
authors.forename: Junzo
authors.initials: J
authors.lastname: Hirono
mesh_terms: D000818:Animals; D000081005:Cyclohexane Monoterpenes; D004192:Discrimination, Psychological; D055879:Gene Knock-In Techniques; D006801:Humans; D007783:Lactones / Q000737:chemistry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D039821:Monoterpenes / Q000737:chemistry; D009812:Odorants / Q000032:analysis*; D018034:Olfactory Receptor Neurons / Q000378:metabolism*; D013237:Stereoisomerism; D014920:Wine / Q000032:analysis
chemical_list: D000081005:Cyclohexane Monoterpenes; D007783:Lactones; D039821:Monoterpenes; C006923:carvone