Pace U, Hanski E, Salomon Y, Lancet D
Nature. 1985;316(6025):255-8. doi: 10.1038/316255a0.
The mechanism of the sense of smell has long been a subject for theory and speculation. More recently, the notion of odorant recognition by stereospecific protein receptors has gained wide acceptance, but the receptor molecules remained elusive. The recognition molecules are believed to be quite diverse, which would partly explain the unusual difficulties encountered in their isolation by conventional ligand-binding techniques. An alternative approach would be to probe the receptors through transductory components that may be common to all receptor types. Here we report the identification of one such transductory molecular component. This is an odorant-sensitive adenylate cyclase, present in very large concentrations in isolated dendritic membranes of olfactory sensory neurones. Odorant activation of the enzyme is ligand and tissue specific, and occurs only in the presence of GTP, suggesting the involvement of receptor(s) coupled to a guanine nucleotide binding protein (G-protein). The olfactory G-protein is independently identified by labelling with bacterial toxins, and found to be similar to stimulatory G-proteins in other systems. Our results suggest a role for cyclic nucleotides in olfactory transduction, and point to a molecular analogy between olfaction and visual, hormone and neurotransmitter reception. Most importantly, the present findings reveal new ways to identify and isolate olfactory receptor proteins.
嗅觉机制长期以来一直是理论和推测的主题。最近，立体特异性蛋白质受体识别气味分子的概念已被广泛接受，但受体分子仍然难以捉摸。人们认为识别分子种类繁多，这在一定程度上解释了用传统配体结合技术分离它们时遇到的异常困难。另一种方法是通过所有受体类型可能共有的转导成分来探测受体。在此我们报告鉴定出一种这样的转导分子成分。这是一种对气味敏感的腺苷酸环化酶，在嗅觉感觉神经元的分离树突膜中大量存在。该酶的气味激活具有配体和组织特异性，并且仅在存在鸟苷三磷酸（GTP）的情况下发生，这表明涉及与鸟嘌呤核苷酸结合蛋白（G蛋白）偶联的受体。嗅觉G蛋白通过用细菌毒素标记而被独立鉴定，并发现与其他系统中的刺激性G蛋白相似。我们的结果表明环核苷酸在嗅觉转导中起作用，并指出嗅觉与视觉、激素和神经递质受体之间存在分子类比。最重要的是，目前的研究结果揭示了识别和分离嗅觉受体蛋白的新方法。
