Roles of P2X7 receptor in glial and neuroblastoma cells: the therapeutic Potential of P2X7 receptor antagonists.

摘要

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+)](i)). 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.