Decreased olfactory mucus secretion and nasal abnormality in mice lacking type 2 and type 3 IP3 receptors
Decreased olfactory mucus secretion and nasal abnormality in mice lacking type 2 and type 3 IP3 receptors
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DOI：
10.1111/j.1460-9568.2008.06240.x
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发表时间：
2008-05-01
影响因子：
3.4
通讯作者：
Mikoshiba, Katsuhiko
中科院分区：
文献类型：
--
作者：
Fukuda, Nanaho;Shirasu, Mika;Mikoshiba, Katsuhiko
虽然鼻粘液被认为在哺乳动物嗅觉系统中起重要作用，但其分泌机制及其生理作用知之甚少。在这里，我们表明，2型和3型IP 3受体（IP 3R 2和IP 3R 3）在嗅觉粘液分泌中起着关键作用。组织学研究表明，IP 3R 2和IP 3R 3主要在两种类型的鼻腺中表达，即鼻中隔前腺和侧鼻腺（LNG），其含有分泌到主要嗅觉上皮的粘膜蛋白。因此，我们检查了LNG腺泡细胞，并发现乙酰胆碱介导的钙反应和液体和蛋白质分泌的腺泡细胞显着减少IP 3R 2-R3双敲除（KO）小鼠。我们还发现IP 3R 2-R3 KO小鼠的鼻腔炎症和嗅觉能力下降。尽管完整的信号转导嗅觉上皮，IP 3R 2-R3基因敲除小鼠表现出提高阈值敏感性气味在体内成像的嗅觉肾小球反应和行为测试。我们的研究结果表明，IP 3R 2和IP 3R 3介导鼻粘液分泌，这对于维持鼻组织以及气味的感知很重要。
Although nasal mucus is thought to play important roles in the mammalian olfactory system, the mechanisms of secretion of it and its physiological roles are poorly understood. Here we show that type 2 and type 3 IP3 receptors (IP3R2 and IP3R3) play critical roles in olfactory mucus secretion. Histological studies showed that IP3R2 and IP3R3 are predominantly expressed in two types of nasal glands, the anterior glands of the nasal septum and the lateral nasal glands (LNG), which contain mucosal proteins secreted to the main olfactory epithelium. We therefore examined LNG acinar cells, and found that acetylcholine-mediated calcium responses and fluid- and protein- secretion in the acinar cells were markedly decreased in IP3R2-R3 double-knockout (KO) mice. We also found nasal inflammation and a decrease in olfactory capacity in IP3R2-R3 KO mice. Despite intact signal transduction in the olfactory epithelium, IP3R2-R3 KO mice exhibited elevated threshold sensitivity to odorants on in vivo imaging of olfactory glomerular responses and behavioral tests. Our findings suggest that IP3R2 and IP3R3 mediate nasal mucus secretion, which is important for the maintenance of nasal tissue as well as the perception of odors.