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Mechanism of odorant adaptation in the olfactory receptor cell

机译：嗅觉受体细胞中气味适应的机制

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摘要

Adaptation to odorants begins at the level of sensory receptor cells, presumably through modulation of their transduction machinery. The olfactory signal transduction involves the activation of the adenylyl cyclase/cyclic AMP second messenger system which leads to the sequential opening of cAMP-gated channels and Ca2+-activated chloride ion channels. Several reports of results obtained from in vitro preparations describe the possible molecular mechanisms involved in odorant adaptation; namely, ordorant receptor phosphorylation, activation of phosphodiesterase, and ion channel regulation. However, it is still unknown whether these putative mechanisms work in the intact olfactory receptor cell. Here we investigate the nature of the adaptational mechanism in intact olfactory cells by using a combination of odorant stimulation and caged cAMP photolysis which produces current responses that bypass the early stages of signal transduction (involving the receptor, G protein and adenylyl cyclase). Odorant- and cAMP-induced responses showed the same adaptation in a Ca2+-dependent manner, indicating that adaptation occurs entirely downstream of the cyclase. Moreover, we show that phosphodiesterase activity remains constant during adaptation and that an affinity change of the cAMP-gated channel for ligands accounts well for our results. We conclude that the principal mechanism underlying odorant adaptation is actually a modulation of the cAMP-gated channel by Ca2+ feedback.
机译：对气味物质的适应始于感觉受体细胞的水平，大概是通过调节它们的转导机制。嗅觉信号转导涉及腺苷酸环化酶/环状AMP第二信使系统的激活，这导致cAMP门控通道和Ca2 +激活的氯离子通道的顺序打开。从体外制剂获得的结果的几份报告描述了气味适应过程可能涉及的分子机制；即，雄性受体磷酸化，磷酸二酯酶活化和离子通道调节。然而，仍不清楚这些推定的机制是否在完整的嗅觉受体细胞中起作用。在这里，我们通过结合气味刺激和笼式cAMP光解来研究完整嗅觉细胞中适应机制的性质，该过程产生电流响应，绕过信号转导的早期阶段（涉及受体，G蛋白和腺苷酸环化酶）。气味和cAMP诱导的反应以Ca2 +依赖性方式显示出相同的适应性，表明适应性完全发生在环化酶的下游。此外，我们表明磷酸二酯酶活性在适应过程中保持恒定，并且cAMP门控通道对配体的亲和力变化很好地说明了我们的结果。我们得出结论，气味适应的基本机制实际上是Ca2 +反馈对cAMP门控通道的调节。

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