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Supersensitive detection and discrimination of enantiomers by dorsal olfactory receptors: evidence for hierarchical odour coding

机译:背嗅受体对映异构体的超灵敏检测和鉴别:分层气味编码的证据

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摘要

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 108-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 >1010-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.
机译:镜像分子结构的对映体对很难通过仪器分析来解析。然而,人类的嗅觉系统会在几秒钟内迅速将(-)-葡萄酒内酯与其(+)形式区分开。为了深入了解对映体的受体编码,我们将野生型小鼠的行为检测阈值和区分阈值与所有背嗅受体均被遗传消除的ΔD小鼠进行了比较。出乎意料的是,野生型小鼠对葡萄酒内酯和酮类的对映体对表现出出色的“超敏性”。他们具有对映异构体的超灵敏识别能力,与其高检测灵敏度相符。相比之下,ΔD小鼠表现出对(+)-对映异构体敏感性的选择性主要损失。所得的ΔD小鼠对(-)-与(+)-葡萄酒内酯的10 8 差异敏感性与人类观察到的相近。这表明,与ΔD小鼠类似,人类缺乏对(+)-对映体的高度敏感的直系背受体。此外,与野生型小鼠相比,ΔD小鼠对映体识别敏感性降低了> 10 10 倍。 ΔD小鼠在较宽的浓度范围内检测到(-)-和(+)-对映体中的一种或两种,但无法区分它们。这种“对映异构体气味辨别悖论”表明,最敏感的背侧受体在识别对映异构体的分层气味编码中起关键作用。

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