Leukemia inhibitory factor and ciliary neurotrophic factor regulate expression of muscarinic receptors in cultured sympathetic neurons.
Leukemia inhibitory factor and ciliary neurotrophic factor regulate expression of muscarinic receptors in cultured sympathetic neurons.
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白血病抑制因子和睫状神经营养因子调节培养的交感神经元中毒蕈碱受体的表达。
DOI：
10.1006/dbio.1993.1047
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发表时间：
1993
影响因子：
2.7
通讯作者：
Kessler,JA
中科院分区：
文献类型：
--
作者：
Ludlam,WH;Kessler,JA
研究了在培养的新生大鼠颈上神经节交感神经元中毒蕈碱受体表达的调控。白血病抑制因子（LIF）和睫状体神经营养因子（CNTF）均可调节培养的SCG神经元中的神经递质发育（Yamamoriet al., 1989; Saadatet al., 1989），研究了它们对受体表达的影响。通过n -甲基[3H]东莨菪碱的全细胞结合测量，SCG神经元暴露于LIF或CNTF （5 ng/ml）中可以阻止毒碱受体的正常发育增加。在治疗2 - 4天内检测到受体结合减少，16天后减少65-80%。Scatchard分析显示，总受体数量（Bmax）减少，但受体亲和力（Kd）无显著变化。任一因子浓度为1 ng/ml时，均可降低受体表达，且在剂量为10 ng/ml时效果接近最大。阿托品没有阻断毒蕈碱受体的减少，表明它不是激动剂诱导的。用LIF或CNTF处理不影响培养神经元的存活。此外，停止治疗后对受体表达的影响是可逆的。最后，用任何一种因子处理都增加了总蛋白质合成，表明培养物的细胞代谢的完整性，从而表明毒蕈碱受体数量减少的特异性。因此，LIF和CNTF调节受体和神经递质发育，因此可能在发育中的神经系统突触发生过程中发挥作用。
Regulation of muscarinic receptor expression was studied in cultured sympathetic neurons of the neonatal rat superior cervical ganglion (SCG). Leukemia inhibitory factor (LIF) and ciliary neurotrophic factor (CNTF), both previously shown to regulate neurotransmitter development in cultured SCG neurons (Yamamoriet al., 1989; Saadatet al., 1989), were examined for effects on receptor expression. Exposure of SCG neurons to LIF or CNTF (5 ng/ml) prevented the normal developmental increase in muscarinic receptors as measured by whole cell binding ofN-methyl[3H]scopolamine. Reduction in receptor binding was detected within 2 to 4 days of treatment, with a 65-80% reduction after 16 days. Scatchard analysis demonstrated a reduction in total receptor number (Bmax) with no significant change in receptor affinity (Kd). Concentrations of 1 ng/ml of either factor reduced receptor expression with near-maximal effectiveness at doses of 10 ng/ml. The decrease in muscarinic receptors was not blocked by atropine, indicating that it was not agonist induced. Treatment with LIF or CNTF did not affect the survival of cultured neurons. Further, effects on receptor expression were reversible after discontinuance of treatment. Finally, treatment with either factor increased overall protein synthesis, indicating the integrity of cellular metabolism of cultures and hence the specificity of the decrease in muscarinic receptor number. LIF and CNTF thus regulate receptor as well as neurotransmitter development and could therefore play a role during synaptogenesis in the developing nervous system.