A pharmacological profile of the aldehyde receptor repertoire in rat olfactory epithelium
A pharmacological profile of the aldehyde receptor repertoire in rat olfactory epithelium
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DOI：
10.1113/jphysiol.2003.058040
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发表时间：
2004-03-16
影响因子：
5.5
通讯作者：
Firestein, S
中科院分区：
文献类型：
--
作者：
Araneda, RC;Peterlin, Z;Firestein, S
几条证据表明，气味是通过嗅觉系统中的组合过程识别的;单个气味被多个受体识别，多个气味被同一受体识别。然而，对于任何特定的气味集合或受体家族，这可能实际上如何起作用的细节很少。从配体而不是受体来处理这个问题，我们使用对常见气味剂辛醛的反应作为定义多个受体谱的基础。辛醛和其他醛类在啮齿动物嗅上皮中诱导大的EOG反应，表明这些化合物激活大量的气味受体（OR）。在这里，我们已经确定并比较了不同的辛醛受体的药理学概况，在孤立的嗅觉感觉神经元（OSNs）中使用钙离子成像。据信，每个OSN仅表达一种受体，因此每个细胞的反应谱对应于一种特定受体的药理学谱。我们用一组九种气味剂刺激细胞，其中包括辛醛、辛酸、辛醇和肉桂醛等（均为30 μ m）。聚类分析揭示了几个不同的药理学档案的细胞都是敏感的辛醛。一些受体具有广泛的分子范围，而另一些受体仅被辛醛激活。与一个确定的辛醛受体，OR-17的配置文件的比较，表明几个差异。虽然OR-17被低浓度的辛醛激活并被柠檬醛阻断，但其他受体对辛醛不太敏感并且不被柠檬醛阻断。辛醛受体的最大数量的较低估计值在33和55之间。辛醛受体的数量之多表明，虽然外周嗅觉系统具有很高的灵敏度，但不同化合物之间的辨别可能需要进一步的中枢处理。
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 Ca2+ 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 30 mum). 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-17, indicated several differences. While OR-17 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.