Nicotinic acetylcholine receptor-mediated release of [3H]norepinephrine from developing and adult rat hippocampus: direct and indirect mechanisms.
Nicotinic acetylcholine receptor-mediated release of [3H]norepinephrine from developing and adult rat hippocampus: direct and indirect mechanisms.
复制标题
烟碱乙酰胆碱受体介导的[3H]去甲肾上腺素从发育中和成年大鼠海马的释放：直接和间接机制。
DOI：
10.1016/s0028-3908(02)00019-9
复制
发表时间：
2002
影响因子：
4.7
通讯作者：
Park,MK
中科院分区：
文献类型：
--
作者：
Leslie,FM;Gallardo,KA;Park,MK
烟碱型乙酰胆碱受体在成人和发育中的脑中的主要作用是调节神经传递。使用体外神经递质释放，我们已经研究了尼古丁诱导的[3 H]去甲肾上腺素释放从发育和成年大鼠海马的机制。出生时，尼古丁显著刺激海马[3 H]去甲肾上腺素释放，在出生后前10天内最大药物效应单调增加。未观察到激动剂或拮抗剂效价的发育变化。比较突触体和切片制备，以及河豚毒素的影响，表明至少有两个烟碱乙酰胆碱受体调节[3 H]去甲肾上腺素释放的新生儿和成人海马，一个本地化的去甲肾上腺素能终端，其他相邻的细胞。为了进一步表征尼古丁在成人中作用的间接机制，我们研究了药理学阻断向海马去甲肾上腺素能末梢提供兴奋性输入的各种神经递质系统的作用。而谷氨酸和毒蕈碱受体阻滞剂是无效的，GABA-A受体拮抗剂，荷包牡丹碱和印防己毒素，抑制尼古丁介导的[3 H]去甲肾上腺素释放的间接成分。此外，GABA-A受体的变构效应物戊巴比妥可增强次最大浓度尼古丁的作用。这些发现与尼古丁诱导的GABA释放作为大鼠海马内[3 H]去甲肾上腺素分泌的额外刺激的假设是一致的。
The primary role of nicotinic acetylcholine receptors in adult and developing brain is to modulate neurotransmission. Using in vitro neurotransmitter release, we have examined mechanisms underlying nicotine-induced [3H]norepinephrine release from developing and adult rat hippocampus. At birth, nicotine significantly stimulated hippocampal [3H]norepinephrine release with a monotonic increase in maximal drug effect over the first ten postnatal days. No developmental changes in agonist or antagonist potency were observed. Comparison of synaptosomal and slice preparations, as well as examination of the effects of tetrodotoxin, indicated that at least two nicotinic acetylcholine receptor populations regulated [3H]norepinephrine release from neonatal and adult hippocampus; one localized on noradrenergic terminals, the other on adjacent cells. To further characterize the indirect mechanism of nicotine action in the adult, we examined the effects of pharmacological blockade of various neurotransmitter systems that provide excitatory input to hippocampal noradrenergic terminals. Whereas glutamate and muscarinic receptor blockade was ineffective, the GABA-A receptor antagonists, bicuculline and picrotoxin, inhibited the indirect component of nicotine-mediated [3H]norepinephrine release. Furthermore, pentobarbital, an allosteric effector at GABA-A receptors, potentiated the effect of submaximal concentrations of nicotine. These findings are consistent with the hypothesis that nicotine-induced GABA release serves as an additional stimulus for [3H]norepinephrine secretion within rat hippocampus.