Biochemistry Department, Institute of General and Molecular Biology, Nicolaus Copernicus University, 7 Gagarina St, 87-100 Torun, Poland.
Acta Vet Scand. 2011 Oct 13;53(1):54. doi: 10.1186/1751-0147-53-54.
Numerous signaling pathways function in the brain ventricular system, including the most important - GABAergic, glutaminergic and dopaminergic signaling. Purinergic signalization system - comprising nucleotide receptors, nucleotidases, ATP and adenosine and their degradation products - are also present in the brain. However, the precise role of nucleotide signalling pathway in the ventricular system has been not elucidated so far. The aim of our research was the identification of all three elements of purinergic signaling pathway in the porcine brain ventricular system.
Besides nucleotide receptors on the ependymocytes surface, we studied purines and pyrimidines in the CSF, including mechanisms of nucleotide signaling in the swine model (Sus scrofa domestica). The results indicate presence of G proteins coupled P2Y receptors on ependymocytes and also P2X receptors engaged in fast signal transmission. Additionally we found in CSF nucleotides and adenosine in the concentration sufficient to P receptors activation. These extracellular nucleotides are metabolised by adenylate kinase and nucleotidases from at least two families: NTPDases and NPPases. A low activity of these nucleotide metabolising enzymes maintains nucleotides concentration in ventricular system in micromolar range. ATP is degraded into adenosine and inosine.
Our results confirm the thesis about cross-talking between brain and ventricular system functioning in physiological as well as pathological conditions. The close interaction of brain and ventricular system may elicit changes in qualitative and quantitative composition of purines and pyrimidines in CSF. These changes can be dependent on the physiological state of brain, including pathological processes in CNS.
许多信号通路在脑室内系统中发挥作用,包括最重要的 GABA 能、谷氨酰胺能和多巴胺能信号通路。嘌呤能信号转导系统 - 包括核苷酸受体、核苷酸酶、ATP 和腺苷及其降解产物 - 也存在于大脑中。然而,迄今为止,核苷酸信号通路在脑室系统中的精确作用尚未阐明。我们研究的目的是鉴定猪脑室内系统中嘌呤能信号通路的所有三个元素。
除了室管膜细胞表面的核苷酸受体外,我们还研究了 CSF 中的嘌呤和嘧啶,包括猪模型(Sus scrofa domestica)中核苷酸信号转导的机制。结果表明,在室管膜细胞上存在与 G 蛋白偶联的 P2Y 受体,也存在参与快速信号转导的 P2X 受体。此外,我们还发现 CSF 中存在足以激活 P 受体的核苷酸和腺苷浓度。这些细胞外核苷酸由至少两种家族的腺苷酸激酶和核苷酸酶代谢:NTPDases 和 NPPases。这些核苷酸代谢酶的低活性使脑室系统中的核苷酸浓度保持在微摩尔范围内。ATP 降解为腺苷和肌苷。
我们的结果证实了脑和脑室系统在生理和病理条件下相互作用的理论。脑和脑室系统的密切相互作用可能会引起 CSF 中嘌呤和嘧啶的定性和定量组成发生变化。这些变化可能取决于脑的生理状态,包括中枢神经系统的病理过程。