The chemosensory system of any animal relies on a vast array of detectors tuned to distinct chemical cues. Odorant receptors and the ion channels of the TRP family are all uniquely expressed in olfactory tissues in a species-specific manner. Great effort has been made to characterize the molecular and pharmacological properties of these proteins. Nevertheless, most of the natural ligands are highly hydrophobic molecules that are not amenable to controlled delivery. We sought to develop photoreleasable, biologically inactive odorants that could be delivered to the target receptor or ion channel and effectively activated by a short light pulse. Chemically distinct ligands eugenol, benzaldehyde, 2-phenethylamine, ethanethiol, butane-1-thiol, and 2,2-dimethylethane-1-thiol were modified by covalently attaching the photoremovable protecting group (8-cyano-7-hydroxyquinolin-2-yl)methyl (CyHQ). The CyHQ derivatives were shown to release the active odorant upon illumination with 365 and 405 nm light. We characterized their bioactivity by measuring activation of recombinant TRPV1 and TRPA1 ion channels expressed in HEK 293 cells and the electroolfactogram (EOG) response from intact mouse olfactory epithelium (OE). Illumination with 405 nm light was sufficient to robustly activate TRP channels within milliseconds of the light pulse. Photoactivation of channels was superior to activation by conventional bath application of the ligands. Photolysis of the CyHQ-protected odorants efficiently activated an EOG response in a dose-dependent manner with kinetics similar to that evoked by the vaporized odorant amyl acetate (AAc). We conclude that CyHQ-based, photoreleasable odorants can be successfully implemented in chemosensory research.

中文翻译：

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用于化学传感研究的可光活化气味。

任何动物的化学感应系统都依赖于多种检测器，这些检测器已根据不同的化学提示进行了调整。气味受体和TRP家族的离子通道均以物种特异性方式在嗅觉组织中唯一表达。为了表征这些蛋白质的分子和药理特性，已经付出了巨大的努力。然而，大多数天然配体是高度疏水的分子，不适合受控递送。我们寻求开发可释放光的，生物惰性的增香剂，该增香剂可以递送至目标受体或离子通道并通过短光脉冲有效激活。化学上不同的配体丁子香酚，苯甲醛，2-苯乙胺，乙硫醇，丁烷-1-硫醇和2，通过将可光去除的保护基团（8-氰基-7-羟基喹啉-2-基）甲基（CyHQ）共价连接来修饰2-二甲基乙烷-1-硫醇。CyHQ衍生物经365和405 nm光照射后释放出活性增香剂。我们通过测量在HEK 293细胞中表达的重组TRPV1和TRPA1离子通道的激活以及完整小鼠嗅觉上皮细胞（OE）的电嗅觉图（EOG）响应来表征其生物活性。405 nm的光照明足以在光脉冲的毫秒内稳固激活TRP通道。通道的光活化优于通过常规配体浴的活化。CyHQ保护的增香剂的光解以剂量依赖的方式有效激活了EOG响应，其动力学与蒸发的增香剂乙酸戊酯（AAc）相似。我们得出的结论是，基于CyHQ的可光释放的增香剂可以在化学传感研究中成功实现。