Enhanced nicotinic acetylcholine receptor-mediated [3H]norepinephrine release from neonatal rat hypothalamus.
Enhanced nicotinic acetylcholine receptor-mediated [3H]norepinephrine release from neonatal rat hypothalamus.
复制标题
增强烟碱乙酰胆碱受体介导的[3H]去甲肾上腺素从新生大鼠下丘脑的释放。
DOI：
10.1016/j.neuropharm.2005.08.013
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Leslie,FM
中科院分区：
文献类型：
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作者：
O'Leary,KT;Leslie,FM
烟碱型乙酰胆碱受体（nAChR）诱发的去甲肾上腺素（NE）释放已被证明在许多接受来自蓝斑（LC）的唯一去甲肾上腺素能神经支配的脑区域中。许多这些结构显示增强尼古丁刺激NE释放的新生儿。我们已经检查了下丘脑，以确定该地区，它接收NE的预测从LC和髓质的儿茶酚胺能核，也表现出成熟的变化nAChR介导的NE释放。定量放射性标记NE释放大鼠下丘脑切片的最大有效剂量的尼古丁显示在出生后第一周的峰值反应。随后在出生后第14天（P）下降，并在P21出现第二个峰值。此后，释放与P14时观察到的释放相当。比较nAChRs介导NE释放在新生儿（P7）和成熟的下丘脑的药理学特性表明参与不同的nAChR亚型在两个年龄。使用选择性毒素DSP-4，nAChR介导的NE释放在新生儿下丘脑被证明是从LC终端。我们的研究结果表明，下丘脑LC终端nAChR的调节，可能与发展的系统控制的关键稳态功能，如压力，喂养和心血管调节的早期敏感性。
Nicotinic acetylcholine receptor (nAChR)-evoked release of norepinephrine (NE) has been demonstrated in a number of brain regions that receive sole noradrenergic innervation from the locus coeruleus (LC). Many of these structures display enhanced nicotine-stimulated NE release in the neonate. We have examined the hypothalamus in order to determine if this region, which receives NE projections from both the LC and medullary catecholaminergic nuclei, also demonstrates maturational changes in nAChR-mediated NE release. Quantification of radiolabeled-NE release from rat hypothalamus slices by a maximally effective dose of nicotine revealed a peak response during the first postnatal week. This was followed by a decrease at postnatal day (P) 14, and a second peak at P21. Thereafter, release was equivalent to that observed at P14. Comparison of the pharmacological properties of nAChRs mediating NE release in neonatal (P7) and mature hypothalamus suggested involvement of different nAChR subtypes at the two ages. Using the selective toxin, DSP-4, nAChR-mediated NE release in the neonatal hypothalamus was shown to be from LC terminals. Our findings demonstrate an early sensitivity of hypothalamic LC terminals to nAChR regulation that may be associated with development of systems controlling critical homeostatic functions such as stress, feeding and cardiovascular regulation.