Department of Medical Pharmacology, CNR Institute of Neuroscience, University of Milan, Via Vanvitelli 32, 20129, Milan, Italy.
Purinergic Signal. 2009 Jun;5(2):233-40. doi: 10.1007/s11302-009-9137-3. Epub 2009 Mar 12.
P2X(7) receptor is a ligand-gated ion channel, which can induce the opening of large membrane pores. Here, we provide evidence that the receptor induces pore formation in astrocytes cultured from cortex, but not from the hippocampus. Furthermore, P2X(7) receptor activation promptly induces p38 mitogen-activated protein kinase (MAPK) phosphorylation in cortical but not in hippocampal astrocytes. Given the role of p38 MAPK activation in pore opening, these data suggest that defective coupling of the receptor to the enzyme could occur in hippocampal cultures. The different capabilities of the receptor to open membrane pores cause relevant functional consequences. Upon pore formation, caspase-1 is activated and pro-IL1-beta is cleaved and released extracellularly. The receptor stimulation does not result in interleukin-1beta secretion from hippocampal astrocytes, although the pro-cytokine is present in the cytosol of lipopolysaccharide-primed cultures. These results open the possibility that activation of P2X(7) receptors differently influences the neuroinflammatory processes in distinct brain regions.
P2X(7) 受体是一种配体门控离子通道，可诱导大膜孔的开放。在这里，我们提供的证据表明，该受体可诱导皮质而非海马体培养的星形胶质细胞形成孔。此外，P2X(7) 受体的激活可迅速诱导皮质而非海马星形胶质细胞中 p38 丝裂原活化蛋白激酶 (MAPK) 的磷酸化。鉴于 p38 MAPK 激活在孔形成中的作用，这些数据表明，在海马体培养物中，受体与酶的偶联可能存在缺陷。受体打开膜孔的不同能力会导致相关的功能后果。在形成孔后，半胱天冬酶-1 被激活，前白细胞介素-1β被切割并释放到细胞外。尽管在脂多糖预刺激培养物的细胞质中存在前细胞因子，但受体刺激不会导致海马星形胶质细胞中白细胞介素-1β的分泌。这些结果表明，P2X(7) 受体的激活可能以不同的方式影响不同脑区的神经炎症过程。
