Purinergic receptor antagonists inhibit odorant-mediated CREB phosphorylation in sustentacular cells of mouse olfactory epithelium.
Purinergic receptor antagonists inhibit odorant-mediated CREB phosphorylation in sustentacular cells of mouse olfactory epithelium.
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DOI：
10.1186/1471-2202-12-86
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发表时间：
2011-08-22
期刊：
影响因子：
2.4
通讯作者：
Neuhaus EM
中科院分区：
文献类型：
--
作者：
Dooley R;Mashukova A;Toetter B;Hatt H;Neuhaus EM
人们早就知道细胞外核苷酸发挥神经调节作用并参与细胞间信号传导。在嗅觉系统中，ATP由嗅觉神经元释放，外源性ATP可引起支持细胞（嗅觉上皮的非神经元支持细胞）的细胞内钙浓度增加。在这里，我们研究了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信的假设。在这里，我们发现，将小鼠暴露于气味混合物中，会导致嗅觉感觉神经元和支持细胞细胞核中 Ser-133 位点磷酸化的转录因子 CREB 水平显着增加。这种激活依赖于腺苷酸环化酶 III 介导的嗅觉信号传导以及支持细胞上 P2Y 嘌呤能受体的激活。嘌呤能受体拮抗剂抑制气味依赖性 CREB 磷酸化，特别是在支持细胞的细胞核中。我们的结果表明，细胞外核苷酸在介导嗅觉上皮神经元和支持细胞之间响应气味暴露的细胞间通讯方面可能发挥作用。因此，细胞外离子梯度的维持和支持细胞对有毒化学物质的代谢可能受到嗅觉感觉神经元以气味依赖性方式的调节。
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.
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影响因子：
56.9
作者：
JONES, DT;REED, RR
通讯作者：
REED, RR
DOI：
10.1073/pnas.91.19.8890
发表时间：
1994-09-13
影响因子：
11.1
作者：
BRADLEY, J;LI, J;ZINN, K
通讯作者：
ZINN, K
影响因子：
13.8
作者：
KARIN, M;SMEAL, T
通讯作者：
SMEAL, T
影响因子：
6.2
作者：
Hegg, CC;Lucero, MT
通讯作者：
Lucero, MT
影响因子：
64.5
作者：
CHESS, A;SIMON, I;AXEL, R
通讯作者：
AXEL, R