Mapping second messenger systems in the brain: differential localizations of adenylate cyclase and protein kinase C.
Mapping second messenger systems in the brain: differential localizations of adenylate cyclase and protein kinase C.
复制标题
绘制大脑第二信使系统图谱：腺苷酸环化酶和蛋白激酶 C 的差异定位。
DOI：
10.1073/pnas.83.11.4053
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发表时间：
1986
影响因子：
11.1
通讯作者：
Snyder,SH
中科院分区：
文献类型：
--
作者：
Worley,PF;Baraban,JM;DeSouza,EB;Snyder,SH
[~ 3 H]Forskolin和[~ 3 H]phorbol 12，13-dibutyrate分别用于脑片腺苷酸环化酶和磷脂酰肌醇系统的光镜放射自显影。[3 H]毛喉素与脑切片的结合被毛喉素（KD约等于15 nM）有力地取代，并被氟化物和GTP类似物（激活腺苷酸环化酶（Gs）的刺激性GTP结合调节蛋白的试剂）增强。最高的[3 H]毛喉素结合发生在纹状体，黑质，海马和小脑的分子层。病变研究表明，黑质中的结合位点与纹状体传入神经有关，而海马位点定位于颗粒细胞树突和苔藓纤维末端，小脑分子层中的强烈结合主要与颗粒细胞轴突和末端有关。蛋白激酶C介导激素和神经递质的活性，其通过磷脂酰肌醇循环起作用，并被[3 H]佛波醇12，13-二丁酸酯以高亲和力标记。在许多突触，腺苷酸环化酶和蛋白激酶C的地图揭示了相互分布，这可能对突触传递的第二信使调节有影响。
[3H]Forskolin and [3H]phorbol 12,13-dibutyrate have been used to map the adenylate cyclase and phosphatidylinositol systems respectively in brain slices by light-microscopic autoradiography. [3H]Forskolin binding to brain sections is displaced potently by forskolin (KD approximately equal to 15 nM) and is enhanced by fluoride and GTP analogs, agents which activate the stimulatory GTP-binding regulatory protein of adenylate cyclase, Gs. Highest [3H]forskolin binding occurs in the corpus striatum, substantia nigra, hippocampus, and molecular layer of the cerebellum. Lesion studies demonstrate that binding sites in the substantia nigra are associated with striatal afferents, while hippocampal sites are localized to granule cell dendrites and mossy fiber terminals, and the intense binding in the cerebellar molecular layer is largely associated with granule cell axons and terminals. Protein kinase C mediates the activity of hormones and neurotransmitters, which act through the phosphatidylinositol cycle, and is labeled with high affinity by [3H]phorbol 12,13-dibutyrate. At many synapses, maps of adenylate cyclase and protein kinase C reveal reciprocal distributions, which may have implications for second messenger regulation of synaptic transmission.