DARPP-32, a dopamine- and adenosine 3':5'-monophosphate-regulated phosphoprotein enriched in dopamine-innervated brain regions. III. Immunocytochemical localization

DARPP-32, a dopamine- and adenosine 3':5'-monophosphate-regulated phosphoprotein enriched in dopamine-innervated brain regions. III. Immunocytochemical localization
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DOI:
10.1523/jneurosci.04-01-00111.1984
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发表时间:
1984-01
期刊:
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通讯作者:
C. Ouimet;P. Miller;H. Hemmings;S. Walaas;P. Greengard
C. Ouimet;P. Miller;H. Hemmings;S. Walaas;P. Greengard
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其他
文献类型:
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作者:
C. Ouimet;P. Miller;H. Hemmings;S. Walaas;P. Greengard

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已经进行了免疫细胞化学研究,以确定DARPP-32的区域和细胞分布,DARPP-32是一种蛋白质,其磷酸化可以在完整细胞中由多巴胺和cAMP调节。这些免疫细胞化学研究表明DARPP-32主要定位于那些富含多巴胺能神经末梢的脑区。此外,染色模式支持DARPP-32存在于多巴胺感受神经元中的结论,即,这些神经元接受多巴胺输入,并且多巴胺能神经元本身不存在。在尾壳核、丘脑核、嗅结节、终纹床核和杏仁复合体的部分内,所有这些都接收强多巴胺输入,DARPP-32免疫反应性存在于神经元细胞体和树突中。在已知接收来自这些核的投射的脑区域中,斑点(假定的神经末梢)对DARPP-32具有强烈的免疫反应性,但固有的细胞体和树突不具有免疫反应性。这些靶区包括苍白球、腹侧苍白球、脚内核和黑质网状部。在任何多巴胺能核的神经元细胞体或树突中均未检测到免疫反应性。此外,DARPP-32免疫反应的神经末梢在形态学或分布模式上与多巴胺能静脉曲张不相似。许多神经元对DARPP-32呈弱免疫反应性,其中一些发现于明显缺乏多巴胺能输入的区域:在整个新皮质中发现弱标记的神经元细胞体和树突,主要在第VI层和小脑的浦肯野神经元中。DARPP-32免疫反应性也存在于某些胶质细胞中,特别是在正中隆起、弓状核和内侧缰中。目前的免疫细胞化学研究与生物化学研究一起进行(Hemmings,H.C.,小的,A.C. Nairn,D.W. Aswad和P. Greengard(1984)J. Neurosci. 4:99-110; Walaas,S.I.,和P. Greengard(1984)J. Neurosci.第四章:84-98),表明DARPP-32存在于含有D-1受体(与腺苷酸环化酶偶联的多巴胺受体)的多巴胺感受神经元亚类中。DARPP-32可能是通过cAMP及其相关蛋白激酶介导的多巴胺某些作用的有效标记物。
Immunocytochemical studies have been carried out to determine the regional and cellular distribution of DARPP-32, a protein the phosphorylation of which can be regulated by dopamine and cAMP in intact cells. These immunocytochemical studies indicate tha DARPP-32 is localized primarily in those brain regions enriched in dopaminergic nerve terminals. Moreover, the staining pattern supports the conclusion that the DARPP-32 is present in dopaminoceptive neurons, i.e., neurons that receive a dopamine input, and that it is absent from the dopaminergic neurons themselves. Within the caudatoputamen, nucleus accumbens, olfactory tubercle, bed nucleus of the stria terminalis, and portions of the amygdaloid complex, all of which receive a strong dopamine input, DARPP-32 immunoreactivity is present in neuronal cell bodies and dendrites. In brain regions that are known to receive projections from these nuclei, puncta (presumed nerve terminals) are strongly immunoreactive for DARPP-32 but indigenous cell bodies and dendrites are not immunoreactive. These target areas include the globus pallidus, ventral pallidum, entopeduncular nucleus, and the pars reticulata of the substantia nigra. No immunoreactivity is detected in neuronal cell bodies or dendrites in any of the dopaminergic nuclei. Furthermore, nerve terminals immunoreactive for DARPP-32 do not resemble dopaminergic varicosities in either their morphology or their pattern of distribution. Many neurons are weakly immunoreactive for DARPP-32 and some of these are found in areas that apparently lack a dopaminergic input: weakly labeled neuronal cell bodies and dendrites were found throughout the neocortex, primarily in layer VI, and in the Purkinje neurons of the cerebellum. DARPP-32 immunoreactivity is also present in certain glial cells, especially in the median eminence, arcuate nucleus, and medial habenula. The present immunocytochemical studies, taken together with biochemical studies (Hemmings, H.C., Jr., A.C. Nairn, D.W. Aswad, and P. Greengard (1984) J. Neurosci. 4: 99–110; Walaas, S.I., and P. Greengard (1984) J. Neurosci. 4: 84–98) on DARPP- 32, indicate that DARPP-32, is present in the subclass of dopaminoceptive neurons containing D-1 receptors (dopamine receptors coupled to adenylate cyclase). DARPP-32 may be an effective marker for certain of the actions of dopamine that are mediated through cAMP and its associated protein kinase.