Expression of D1 but not D2 dopamine receptors in striatal neurons producing neurokinin B in rats
Expression of D1 but not D2 dopamine receptors in striatal neurons producing neurokinin B in rats
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DOI：
10.1111/j.1460-9568.2007.05923.x
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发表时间：
2007-12
影响因子：
3.4
通讯作者：
T. Sonomura;KouichiC . Nakamura;T. Furuta;H. Hioki;A. Nishi;A. Yamanaka;M. Uemura;T. Kaneko
中科院分区：
文献类型：
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作者：
T. Sonomura;KouichiC . Nakamura;T. Furuta;H. Hioki;A. Nishi;A. Yamanaka;M. Uemura;T. Kaneko
已知的新纹状体投射神经元主要分为纹状体丘脑/纹状体黑质神经元和纹状体苍白球神经元，它们分别主要表达D_1和D_2多巴胺受体。最近，据报道，少数新纹状体神经元产生神经激肽B(NKB)，并将其轴突主要发送到基底前脑区域。为了揭示这些产生NKB的神经元表达哪种类型的多巴胺受体，我们结合免疫荧光标记NKB的前体速激肽原B(PPTB)和多巴胺受体的荧光原位杂交标记来检测大鼠纹状体神经元。在PPTB免疫阳性神经元中，85-89%的新纹状体、伏隔核和纹状体外侧纹状体内检测到D2受体的荧光信号，而PPTB阳性的纹状体神经元几乎没有检测到D2受体的荧光信号。为了进一步揭示PPTB产生神经元中D1受体下游的细胞内信号，我们用双重免疫荧光标记方法研究了已知由D1受体激活的蛋白激酶A(PKA)的一些底物的定位。虽然只有3-7%的PPTB免疫阳性的纹状体神经元对多巴胺和cAMP调节的32 kDa的磷酸蛋白(一种在两大类新的纹状体投射神经元中都有表达的已知PKA底物)呈免疫反应，但60%-的PPTB阳性的纹状体神经元对纹状体富集型酪氨酸磷酸酶呈免疫反应。这些结果表明，产生NKB的新纹状体神经元在多巴胺受体亚型的使用上与纹状体丘脑/纹状体黑质神经元相似，但在多巴胺受体下游信号传递方面与两大类新纹状体投射神经元不同。
Neostriatal projection neurons are known to be largely divided into two groups, striatoentopeduncular/striatonigral and striatopallidal neurons, which mainly express D1 and D2 dopamine receptors, respectively. Recently, a small population of neostriatal neurons have been reported to produce neurokinin B (NKB), and send their axons mainly to the basal forebrain regions. To reveal which type of dopamine receptors were expressed by these NKB‐producing neurons, we examined rat striatal neurons by combining immunofluorescence labeling for preprotachykinin B (PPTB), the precursor of NKB, and fluorescence in situ hybridization labeling for dopamine receptors. Fluorescent signals for D1 receptor mRNA were detected in 85–89% of PPTB‐immunopositive neurons in the neostriatum, accumbens nucleus and lateral stripe of the striatum, whereas almost no signal for D2 receptor was observed in PPTB‐positive striatal neurons. To further reveal intracellular signaling downstream of D1 receptor in PPTB‐producing neurons, we used a double immunofluorescence labeling method to study the localization of some substrates for protein kinase A (PKA), which was known to be activated by D1 receptor. Although only 3–7% of PPTB‐immunopositive striatal neurons displayed immunoreactivity for dopamine‐ and cAMP‐regulated phosphoprotein of 32 kDa, a well‐known PKA substrate expressed in the two major groups of neostriatal projection neurons, 60–64% of PPTB‐positive striatal neurons exhibited immunoreactivity for striatal‐enriched tyrosine phosphatase. These results suggest that NKB‐producing neostriatal neurons are similar to striatoentopeduncular/striatonigral neurons in the usage of dopamine receptor subtypes, but different from the two major groups of neostriatal projection neurons in terms of the downstream signaling of dopamine receptors.