Institute of Neuroscience, National Yang Ming University, Taipei, Taiwan, Republic of China.
Mol Neurobiol. 2010 Jun;41(2-3):351-5. doi: 10.1007/s12035-010-8120-x. Epub 2010 Apr 21.
Recently, one of the P2 purinergic receptors, the P2X(7) receptor, has been extensively studied in nervous system and important functions have been revealed in both astrocytes and microglia. Stimulation of the receptors induces a sustained and nondesensitized increase in intracellular Ca(2+) concentration (Ca(2+)). In astrocytes purinergic receptors primarily regulate neurotransmission by inducing gliotransmitters release whereas in microglia the receptors stimulate the processing and release of proinflammation cytokines such as interleukin-1 and are thereby involved in inflammation and neurodegeneration. Thus, P2X(7) receptors are considered not only to exert physiological functions but also mediate cell death. P2X(7) receptors have also been identified in various cancer cells and in neuroblastoma cells. In these cells, the P2X(7) receptor-mediated sustained Ca(2+) signal is important in maintaining cellular viability and growth. Accordingly, these findings not only lead to a better understanding of roles of the receptor but also prompt the development of more potent, selective and safer P2X(7) selective antagonists. These emerging antagonists bring new hope in the treatment of inflammatory-induced neurodegenerative diseases as well as neuroblastoma.
最近，嘌呤能 P2 受体家族中的一员，P2X（7）受体，在神经系统中的作用受到了广泛研究，其在星形胶质细胞和小胶质细胞中发挥着重要作用。该受体被激活后可引起细胞内钙离子浓度（[Ca（2+）]（i））持续、非脱敏增加。在星形胶质细胞中，嘌呤能受体主要通过诱导神经递质释放来调节神经递质传递；而在小胶质细胞中，受体刺激前炎症细胞因子（如白细胞介素-1）的加工和释放，从而参与炎症和神经退行性变。因此，P2X（7）受体不仅被认为具有生理功能，还介导细胞死亡。P2X（7）受体也已在各种癌细胞和神经母细胞瘤中被鉴定出来。在这些细胞中，P2X（7）受体介导的持续 Ca（2+）信号对于维持细胞活力和生长非常重要。因此，这些发现不仅有助于更好地了解受体的作用，还促使开发出更有效、选择性更强、安全性更高的 P2X（7）选择性拮抗剂。这些新出现的拮抗剂为治疗炎症诱导的神经退行性疾病以及神经母细胞瘤带来了新的希望。
