Effects of ciliary neurotrophic factor (CNTF) and depolarization on neuropeptide expression in cultured sympathetic neurons.

Effects of ciliary neurotrophic factor (CNTF) and depolarization on neuropeptide expression in cultured sympathetic neurons.
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睫状神经营养因子(CNTF)和去极化对培养交感神经元神经肽表达的影响。

DOI:
10.1016/0012-1606(92)90242-9
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发表时间:
1992
影响因子:
2.7
通讯作者:
Patterson,PH
Patterson,PH
中科院分区:
生物学3区
文献类型:
--
作者:
Rao,MS;Tyrrell,S;Landis,SC;Patterson,PH

文献摘要

被引文献

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我们检测了睫状神经营养因子(CNTF)和去极化这两种影响去甲肾上腺素能和胆碱能功能的环境信号对培养交感神经元神经肽表达的影响。坐骨神经提取物是CNTF的丰富来源,可使血管活性肠肽(VIP)、P物质和生长抑素的水平增加数倍,同时显著降低神经肽Y (NPY)的水平。leu-enkephalin (L-Enk)水平未见变化。重组CNTF的抗血清免疫沉淀提取的CNTF样分子消除了这些作用,重组CNTF引起的神经肽水平变化与坐骨神经提取物相似。CNTF对神经肽水平的改变呈剂量依赖性,浓度为5-25 ng/ml时最大。仅在CNTF暴露3天后,肽水平就发生了变化,并持续了14天。高钾交感神经元去极化培养引起不同的效应谱;它增加了VIP和NPY的含量,但没有改变P物质、生长抑素和L-Enk。众所周知,去极化可以阻断胆碱能对心脏细胞条件培养基的诱导,我们发现它可以阻断重组胆碱能分化因子/白血病抑制因子(CDF/LIF)对胆碱乙酰转移酶(ChAT)和肽的诱导。相反,它不会拮抗CNTF对ChAT活性或神经肽表达的影响。因此,尽管CNTF对神经递质性质的影响与之前报道的CDF/LIF相似,但这两种因子的作用通过去极化调节是不同的,这表明这两种因子的胆碱能和神经肽诱导机制不同。此外,与CDF/LIF相比,CNTF不改变培养背根神经节神经元中ChAT、VIP、P物质或生长抑素的水平。这些观察结果表明,CNTF和去极化影响了交感神经元神经肽的表达,并为CNTF和CDF/LIF这两种神经元分化因子的重叠但不同的作用谱提供了证据。
We examined the effects of ciliary neurotrophic factor (CNTF) and depolarization, two environmental signals that influence noradrenergic and cholinergic function, on neuropeptide expression by cultured sympathetic neurons. Sciatic nerve extract, a rich source of CNTF, increased levels of vasoactive intestinal peptide (VIP), substance P, and somatostatin severalfold while significantly reducing levels of neuropeptide Y (NPY). No change was observed in the levels of leu-enkephalin (L-Enk). These effects were abolished by immunoprecipitation of CNTF-like molecules from the extract with an antiserum raised against recombinant CNTF, and recombinant CNTF caused changes in neuropeptide levels similar to those of sciatic nerve extract. Alterations in neuropeptide levels by CNTF were dose-dependent, with maximal induction at concentrations of 5–25 ng/ml. Peptide levels were altered after only 3 days of CNTF exposure and continued to change for 14 days. Depolarization of sympathetic neuron cultures with elevated potassium elicited a different spectrum of effects; it increased VIP and NPY content but did not alter substance P, somatostatin, or L-Enk. Depolarization is known to block cholinergic induction in response to heart cell conditioned medium and we found that it blocked the induction of choline acetyltransferase (ChAT) and peptides by recombinant cholinergic differentiation factor/leukemia inhibitory factor (CDF/LIF). In contrast, it did not antagonize the effects of CNTF on either ChAT activity or neuropeptide expression. Thus, while CNTF has effects on neurotransmitter properties similar to those previously reported for CDF/LIF, the actions of these two factors are differentially modulated by depolarization, suggesting that the mechanisms of cholinergic and neuropeptide induction for the two factors differ. In addition, in contrast to CDF/LIF, CNTF did not alter levels of ChAT, VIP, substance P, or somatostatin in cultured dorsal root ganglion neurons. These observations indicate that CNTF and depolarization affect the expression of neuropeptides by sympathetic neurons and provide evidence for an overlapping yet distinct spectrum of actions of the two neuronal differentiation factors, CNTF and CDF/LIF.