Tissue distribution and physiorogical function of ATP receptors

ATP受体的组织分布和生理功能

基本信息

批准号：
10670092
负责人：
MATSUOKA Isao
金额：
$ 1.92万
依托单位：
Fukushima Medical University, School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

项目摘要

P2 purinoceptor mRNA expression in the central nervous system was examined by the reverse transcription-coupled polymalase chain reaction (RT-PCR) with 11 different P2 receptor subtype-specific primers. Under an optimal condition, P2X_4 and P2X_6 receptors were found to be dominant P2X ionotropic receptors in rat brain. P2X_7 receptor mRNA was also ubiquitously expressed to a lesser extent. P2X_2 and P2X_5 receptor mRNAs exhibited more discrete distribution, localized in midbrain, brain stem and spinal cord. P2 X_3 was only detected in the brain stem and spinal cord. P2X_1 was little expressed in the rat brain. In contrast, G protein-coupled P2Y receptor subtypes were widely distributed in the brain and relative amount was P2Y_1≧P2Y_2≧P2Y_4>P2Y_6. During the postnatal development, P2X_2 receptor mRNA was highly expressed in many brain regions and progressively decreased during the development. In contrast, P2Y_2 and P2Y_6 receptors were increased. These results demonstrate that several P2 receptors were expressed in the rat brain in a region specific and development-dependent manner.On the other hand, a unique ATP-induced response that did not fit with any cloned P2 receptors was found in cell lines derived from the central nervous system. This response was identified as an event occurring in a membrane surface microdomain where extracellular ATP was rapidly and quantitatively converted into adenosine by ectonucleotidases, resulting in activation of P1 adenosine receptors. This ATP-induced response was somewhat more potent than adenosine-induced one. It is therefore suggested that ecto-nucleotidases and P1 receptors are closely localized in the membrane surface, and functionally couple to respond to ATP.

通过逆转录偶联的聚合酶链反应（RT-PCR）与11种不同的P2受体亚型特异性引物检查中枢神经系统中的P2 Purinoceptor mRNA表达。在最佳条件下，发现P2X_4和P2X_6受体是大鼠脑中的主要P2X离子受体。 P2X_7受体mRNA也普遍于较小的程度。 P2X_2和P2X_5受体mRNA暴露了更多离散的分布，位于中脑，脑干和脊髓中。仅在脑干和脊髓中检测到P2X_3。 p2x_1在大鼠大脑中几乎没有表达。相反，G蛋白偶联的P2Y受体亚型被广泛分布在大脑中，相对量为P2Y_1≧P2Y_2≧P2Y_4> P2Y__6。在产后发育期间，P2X_2受体mRNA在许多大脑区域高度表达，相反，P2Y_2和P2Y_6受体增加。这些结果表明，几种P2受体以特定区域和发展依赖性的方式在大鼠脑中表达。另一方面，在来自中枢神经系统的细胞系中发现了一种独特的ATP诱导的反应，与任何克隆的P2受体都不适合。该反应被确定为发生在膜表面微域中的事件，在该事件中，细胞外ATP迅速并定量地通过Econucleotidass将其转化为腺苷，从而导致P1腺苷受体的激活。与腺苷诱导的反应相比，这种ATP诱导的反应更有潜力。因此，提出核核苷酸酶和P1受体紧密定位在膜表面，并在功能上逐渐响应ATP。