Department of Applied Biological Chemistry, The University of Tokyo, Tokyo 113-8675, Japan.
J Neurosci. 2010 Dec 1;30(48):16391-8. doi: 10.1523/JNEUROSCI.2527-10.2010.
Odor information is decoded by a combination of odorant receptors, and thus transformed into discrete spatial patterns of olfactory glomerular activity. It has been found, however, that for some odorants, there are differences between the ligand specificity of an odorant receptor in vitro and its corresponding glomerulus in vivo. These observations led us to hypothesize that there exist prereceptor events that affect the local concentration of a given odorant in the nasal mucus, thus causing the apparent specificity differences. Here we show that odorants with functional groups such as aldehydes and esters are targets of metabolic enzymes secreted in the mouse mucus, resulting in their conversion to the corresponding acids and alcohols. The glomerular activation patterns elicited by an enzyme-targeted odorant in the olfactory bulb was different in the presence of an enzyme inhibitor in the mucosa, suggesting that the enzymatic conversion occurs fast enough to affect recognition of the odorant at the levels of olfactory sensory neurons. Importantly, olfactory discrimination tests revealed that mice behaviorally trained to associate an enzyme-targeted odorant to sugar rewards could not discriminate the odorant after treatment with the enzyme inhibitor. These results reveal that the enzymatic conversion of odorants in the nasal mucus appears be fast enough to affect olfactory perception, which sheds light on the previously unappreciated role of nasal mucosal enzymes in odor sensation.
气味信息是由气味受体组合解码的,因此转化为嗅觉小球活动的离散空间模式。然而,已经发现,对于一些气味剂,气味受体在体外的配体特异性与其体内相应的嗅球之间存在差异。这些观察结果使我们假设存在前受体事件,这些事件会影响鼻粘液中特定气味剂的局部浓度,从而导致明显的特异性差异。在这里,我们表明具有醛和酯等官能团的气味剂是在小鼠粘液中分泌的代谢酶的靶标,导致它们转化为相应的酸和醇。在粘膜中存在酶抑制剂的情况下,嗅球中酶靶向气味剂引起的肾小球激活模式不同,这表明酶转化发生得足够快,足以影响嗅觉感觉神经元水平对气味剂的识别。重要的是,嗅觉辨别测试表明,经过酶抑制剂处理后,经过训练将酶靶向气味剂与糖奖励相关联的小鼠无法辨别该气味剂。这些结果表明,鼻粘液中的气味剂的酶转化速度足够快,足以影响嗅觉感知,这揭示了鼻腔粘膜酶在嗅觉感知中以前未被重视的作用。