Department of Molecular Medicine, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland.
BMC Neurosci. 2011 Aug 22;12:86. doi: 10.1186/1471-2202-12-86.
Extracellular nucleotides have long been known to play neuromodulatory roles and to be involved in intercellular signalling. In the olfactory system, ATP is released by olfactory neurons, and exogenous ATP can evoke an increase in intracellular calcium concentration in sustentacular cells, the nonneuronal supporting cells of the olfactory epithelium. Here we investigate the hypothesis that olfactory neurons communicate with sustentacular cells via extracellular ATP and purinergic receptor activation.
Here we show that exposure of mice to a mixture of odorants induced a significant increase in the levels of the transcription factor CREB phosphorylated at Ser-133 in the nuclei of both olfactory sensory neurons and sustentacular cells. This activation was dependent on adenylyl cyclase III-mediated olfactory signaling and on activation of P2Y purinergic receptors on sustentacular cells. Purinergic receptor antagonists inhibited odorant-dependent CREB phosphorylation specifically in the nuclei of the sustentacular cells.
Our results point to a possible role for extracellular nucleotides in mediating intercellular communication between the neurons and sustentacular cells of the olfactory epithelium in response to odorant exposure. Maintenance of extracellular ionic gradients and metabolism of noxious chemicals by sustentacular cells may therefore be regulated in an odorant-dependent manner by olfactory sensory neurons.
细胞外核苷酸早已被认为在神经调节和细胞间信号传递中发挥作用。在嗅觉系统中，ATP 由嗅觉神经元释放，外源性 ATP 可以引起嗅上皮中非神经元支持细胞——支持细胞内钙离子浓度的增加。在这里，我们假设嗅觉神经元通过细胞外 ATP 和嘌呤能受体激活与支持细胞进行通讯。
我们发现，暴露于气味混合物中的小鼠，其嗅觉感觉神经元和支持细胞细胞核中 CREB 转录因子 Ser-133 磷酸化水平显著增加。这种激活依赖于 adenylyl cyclase III 介导的嗅觉信号转导以及支持细胞上 P2Y 嘌呤能受体的激活。嘌呤能受体拮抗剂特异性抑制支持细胞细胞核中气味依赖性 CREB 磷酸化。
我们的结果表明，细胞外核苷酸可能在嗅觉神经元和嗅上皮支持细胞之间的细胞间通讯中发挥作用，以响应气味暴露。因此，支持细胞可能通过嗅觉感觉神经元以气味依赖性方式调节细胞外离子梯度和有害物质的代谢。
