Abstract
BackgroundNumerous 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.ResultsBesides 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.ConclusionsOur 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.
Highlights
Numerous signaling pathways function in the brain ventricular system, including the most important - GABAergic, glutaminergic and dopaminergic signaling
The aim of our research was to elucidate if all three elements of purinergic signaling pathway, including nucleotide receptors on the ependymocytes surface, purines and pyrimidines in the cerebrospinal fluid (CSF) and mechanisms of nucleotide signal termination, are present in the porcine brain ventricular system
Materials Cerebrospinal fluids (CSFs) of healthy swines were collected in Department of Swine Diseases, National Veterinary Research Institute (Puławy, Poland) following ethical procedures laid by ethical committee of the university
Summary
Numerous signaling pathways function in the brain ventricular system, including the most important - GABAergic, glutaminergic and dopaminergic signaling. It is well known that cerebrospinal fluid transports signaling molecules and trophic factors generating complex physiological responses due to the activation of their appropriate receptors present on the cells contacting the CSF [1,2,3,4]. There are numerous signalization pathways functioning in the brain ventricular system. Ectopurines are involved in the activation of differentiation and neuritogenesis of precursor cells and neurons. They stimulate synthesis and release of trophic factors in neuronal and glial cells and enhance the effect of growth factors [17,18]. The P1 and P2 receptors are colocalized in the most types of cells, where they act antagonistically and regulate the physiological processes [19,22,25,26,27]
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