Araneda Ricardo C, Peterlin Zita, Zhang Xinmin, Chesler Alex, Firestein Stuart
Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
J Physiol. 2004 Mar 16;555(Pt 3):743-56. doi: 10.1113/jphysiol.2003.058040. Epub 2004 Jan 14.
Several lines of evidence suggest that odorants are recognized through a combinatorial process in the olfactory system; a single odorant is recognized by multiple receptors and multiple odorants are recognized by the same receptor. However few details of how this might actually function for any particular odour set or receptor family are available. Approaching the problem from the ligands rather than the receptors, we used the response to a common odorant, octanal, as the basis for defining multiple receptor profiles. Octanal and other aldehydes induce large EOG responses in the rodent olfactory epithelium, suggesting that these compounds activate a large number of odour receptors (ORs). Here, we have determined and compared the pharmacological profile of different octanal receptors using Ca(2+) imaging in isolated olfactory sensory neurones (OSNs). It is believed that each OSN expresses only one receptor, thus the response profile of each cell corresponds to the pharmacological profile of one particular receptor. We stimulated the cells with a panel of nine odorants, which included octanal, octanoic acid, octanol and cinnamaldehyde among others (all at 30microM). Cluster analysis revealed several distinct pharmacological profiles for cells that were all sensitive to octanal. Some receptors had a broad molecular range, while others were activated only by octanal. Comparison of the profiles with that of the one identified octanal receptor, OR-I7, indicated several differences. While OR-I7 is activated by low concentrations of octanal and blocked by citral, other receptors were less sensitive to octanal and not blocked by citral. A lower estimate for the maximal number of octanal receptors is between 33 and 55. This large number of receptors for octanal suggests that, although the peripheral olfactory system is endowed with high sensitivity, discrimination among different compounds probably requires further central processing.
多条证据表明，气味分子是通过嗅觉系统中的组合过程被识别的；单一气味分子可被多种受体识别，而多种气味分子也可被同一受体识别。然而，对于这一过程在任何特定气味组或受体家族中实际如何发挥作用，几乎没有详细信息。我们从配体而非受体的角度来解决这个问题，将对常见气味分子辛醛的反应作为定义多种受体特征的基础。辛醛和其他醛类在啮齿动物嗅觉上皮中可诱发较大的眼电图（EOG）反应，这表明这些化合物能激活大量气味受体（ORs）。在此，我们利用分离的嗅觉感觉神经元（OSNs）中的Ca(2+)成像技术，确定并比较了不同辛醛受体的药理学特征。据信每个OSN仅表达一种受体，因此每个细胞的反应特征对应于一种特定受体的药理学特征。我们用一组九种气味分子刺激细胞，其中包括辛醛、辛酸、辛醇和肉桂醛等（均为30微摩尔）。聚类分析揭示了所有对辛醛敏感的细胞的几种不同药理学特征。一些受体具有广泛的分子范围，而另一些仅被辛醛激活。将这些特征与已鉴定的一种辛醛受体OR-I7的特征进行比较，发现了一些差异。虽然OR-I7可被低浓度的辛醛激活并被柠檬醛阻断，但其他受体对辛醛的敏感性较低且不被柠檬醛阻断。辛醛受体的最大数量的较低估计值在33至55之间。辛醛的大量受体表明，尽管外周嗅觉系统具有高灵敏度，但不同化合物之间的区分可能还需要进一步的中枢处理。
