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食蟹猴脑和神经节中烟碱受体的分布:α3亚基mRNA、α-银环蛇毒素和尼古丁结合位点的定位

Distribution of nicotinic receptors in cynomolgus monkey brain and ganglia: localization of alpha 3 subunit mRNA, alpha-bungarotoxin and nicotine binding sites.

作者信息

Cimino M, Marini P, Fornasari D, Cattabeni F, Clementi F

机构信息

Institute of Pharmacology and Pharmacognosy, University of Urbino, Italy.

出版信息

Neuroscience. 1992 Nov;51(1):77-86. doi: 10.1016/0306-4522(92)90472-e.

DOI:10.1016/0306-4522(92)90472-e
PMID:1465189
Abstract

The distribution of nicotinic receptors in the brain and ganglia of the Cynomolgus monkey was studied by in situ hybridization and receptor autoradiography. A 35S-labeled antisense riboprobe for the mRNA of the alpha 3 subunit of the human nicotinic receptor, [3H]L-nicotine and [125]alpha-bungarotoxin were used as markers. The highest levels of alpha 3-mRNA were observed in the hippocampus, the medial habenula, the lateral geniculate, the granular layer of the cerebellum, as well as in the pineal gland; moderate levels were found in other nuclei of the thalamus and in the deeper layers of the cerebral cortex. High-affinity binding sites for [3H]L-nicotine were observed mainly in the thalamus. The distribution of [125I]alpha-bungarotoxin binding sites was different from that observed for alpha 3-mRNA and [3H]L-nicotine; they were most abundant in a few specific thalamic nuclei, in the medial habenula and in lamina I of the cerebral cortex. The localization of these three markers was also investigated in the sympathetic, parasympathetic and sensory ganglia of the monkey. Intense labeling was observed for alpha 3-mRNA and for [125I]alpha-bungarotoxin in the sympathetic and parasympathetic ganglia, whereas no positive signal was seen in the ganglion of Gasser. [3H]L-nicotine binding was not detected in any of the ganglia examined. High levels of mRNA for the alpha 3 subunit of the nicotinic receptor were also detected in human sympathetic ganglia. Comparison between alpha 3-mRNA distribution and [3H]L-nicotine binding suggests that in the Cynomolgus monkey brain, the alpha 3 subunit may participate in the formation of more than one nicotinic receptor subtype: a high-affinity binding site for [3H]L-nicotine in the thalamus, and other sites with low affinity for nicotine in the medial habenula and cerebral cortex. Both the alpha 3-mRNA and the [125I]alpha-bungarotoxin are highly expressed in the sympathetic ganglia; however, since no information is presently available on the intraneuronal cellular localization, it cannot be established whether or not they are both present at synaptic sites.

摘要

通过原位杂交和受体放射自显影技术,研究了食蟹猴大脑和神经节中烟碱型受体的分布。使用了针对人烟碱型受体α3亚基mRNA的35S标记反义核糖探针、[3H]L-尼古丁和[125I]α-银环蛇毒素作为标记物。在海马体、内侧缰核、外侧膝状体、小脑颗粒层以及松果体中观察到α3-mRNA的最高水平;在丘脑的其他核团和大脑皮层深层发现中等水平。[3H]L-尼古丁的高亲和力结合位点主要在丘脑中观察到。[125I]α-银环蛇毒素结合位点的分布与α3-mRNA和[3H]L-尼古丁的分布不同;它们在少数特定的丘脑核团、内侧缰核和大脑皮层I层中最为丰富。还在猴的交感神经节、副交感神经节和感觉神经节中研究了这三种标记物的定位。在交感神经节和副交感神经节中观察到α3-mRNA和[125I]α-银环蛇毒素的强烈标记,而在三叉神经节中未见到阳性信号。在所检查的任何神经节中均未检测到[3H]L-尼古丁结合。在人交感神经节中也检测到烟碱型受体α3亚基的高水平mRNA。α3-mRNA分布与[3H]L-尼古丁结合之间的比较表明,在食蟹猴大脑中,α3亚基可能参与了不止一种烟碱型受体亚型的形成:丘脑中[3H]L-尼古丁的高亲和力结合位点,以及内侧缰核和大脑皮层中对尼古丁低亲和力的其他位点。α3-mRNA和[125I]α-银环蛇毒素在交感神经节中均高度表达;然而,由于目前尚无关于神经元内细胞定位的信息,因此无法确定它们是否都存在于突触部位。

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