Purinergic receptor activation evokes neurotrophic factor neuropeptide Y release from neonatal mouse olfactory epithelial slices.
Purinergic receptor activation evokes neurotrophic factor neuropeptide Y release from neonatal mouse olfactory epithelial slices.
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DOI：
10.1002/jnr.21954
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发表时间：
2009-05-01
影响因子：
4.2
通讯作者：
Hegg, Colleen Cosgrove
中科院分区：
文献类型：
--
作者：
Kanekar, Shami;Jia, Cuihong;Hegg, Colleen Cosgrove
损伤诱发神经再生机制的一个前提是损伤细胞诱导神经营养因子的释放以触发神经发生。细胞外嘌呤核苷酸通过激活嘌呤受体介导在中枢神经系统中发挥多种神经营养作用。然而，嘌呤能是否在嗅神经上皮中具有神经营养作用尚未研究。因此，我们监测了ATP诱导的神经肽Y（NPY）的释放，这是一种增加嗅上皮神经增殖的神经肽。为了使NPY释放可视化，将来自新生小鼠的嗅上皮切片在硝酸纤维素纸上培养。硝酸纤维素的免疫分析表明，在相应的鼻腔嗅上皮细胞的区域中的NPY免疫反应。暴露于外源性ATP（100，500 µM）1小时后，释放NPY的嗅上皮切片数量从25±6%显著增加至60±7%或71±10%（p=0.001）。嘌呤能受体拮抗剂磷酸吡哆醛-6-偶氮苯基-2 '，4'-二磺酸（PPADS; 25 µM）和苏拉明（100 µM）显著减少了表现出ATP诱发的NPY释放的嗅上皮切片数量至18±11%（p=0.004），表明NPY释放是由嘌呤能受体激活介导的。通过酶和放射免疫测定法定量释放的NPY。外源性ATP或UTP可显著增加NPY的释放量。总的来说，这项研究表明，嘌呤能受体激活介导的神经营养因子神经肽Y在嗅上皮细胞的释放，并提供药理学目标，以促进受损的嗅上皮细胞的再生。
One premise regarding the mechanism of injury-evoked neuroregeneration is that injured cells induce the release of neurotrophic factors to trigger neurogenesis. Extracellular purine nucleotides exert multiple neurotrophic actions in the central nervous system mediated via activation of purinergic receptors. However, whether purinergics have a neurotrophic role in the olfactory neuroepithelium has not been investigated. Thus, we monitored the ATP-induced release of neuropeptide Y (NPY), a neuropeptide that increases neuroproliferation in the olfactory epithelium. To visualize NPY release, slices of olfactory epithelium from neonatal mice were cultured on nitrocellulose paper. Immunoassays of the nitrocellulose demonstrated NPY immunoreactivity in regions corresponding to the olfactory epithelium of the nasal cavity. One hr exposure to exogenous ATP (100, 500 µM) significantly increased the number of olfactory epithelium slices that released NPY from 25±6% to 60±7% or 71±10% (p=0.001). The purinergic receptor antagonists pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS; 25 µM) and suramin (100 µM) significantly reduced the number of olfactory epithelium slices exhibiting ATP-evoked NPY release to 18±11% (p=0.004), indicating that NPY release is mediated by activation of purinergic receptors. Released NPY was quantified by enzyme and radioimmunoassays. Exogenous ATP or UTP significantly increased the amount of NPY released. Collectively, this study demonstrates that purinergic receptor activation mediates the release of neurotrophic factor NPY in the olfactory epithelium and provides pharmacological targets to promote regeneration of damaged olfactory epithelium.
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影响因子：
2.8
作者：
Gaikwad, A;Biju, KC;Subhedar, N
通讯作者：
Subhedar, N
影响因子：
5.3
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Mousley, Angela;Polese, Gianluca;Eisthen, Heather L.
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TAKHAL, S
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Kawauchi, S;Beites, CL;Calof, AL
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