The P2X7 receptor (P2X7R) stands out within the purinergic family as it has exclusive pharmacological and regulatory features, and it fulfills distinct roles depending on the type of stimulation and cellular environment. Tonic activation of P2X7R promotes cell proliferation, whereas sustained activation is associated with cell death. Yet strikingly, prolonged P2X7R activation in rat cerebellar granule neurons and astrocytes does not affect cell survival. The intracellular pathways activated by P2X7Rs involve proteins like MAPKs, ERK1/2 and p38, and interactions with growth factor receptors could explain their behavior in populations of rat cerebellar cells. In this study, we set out to characterize the intracellular mechanisms through which P2X7Rs and Trk receptors, EGFR (epidermal growth factor receptor) and BDNFR (brain-derived neurotrophic factor receptor), regulate the dual-specificity phosphatase DUSP1. In cerebellar astrocytes, the regulation of DUSP1 expression by P2X7R depends on ERK and p38 activation. EGFR stimulation can also induce DUSP1 expression, albeit less strongly than P2X7R. Conversely, EGF was virtually ineffective in regulating DUSP1 in granule neurons, a cell type in which BDNF is the main regulator of DUSP1 expression and P2X7R only induces a mild response. Indeed, the regulation of DUSP1 elicited by BDNF reflects the balance between both transcriptional and post-transcriptional mechanisms. Importantly, when the regulation of DUSP1 expression is compromised, the viability of both astrocytes and neurons is impaired, suggesting this phosphatase is essential to maintain proper cell cytoarchitecture and functioning.

P2X7 受体 (P2X7R) 在嘌呤能家族中脱颖而出，因为它具有独特的药理学和调节特征，并且根据刺激类型和细胞环境发挥不同的作用。 P2X7R 的强直激活可促进细胞增殖，而持续激活则与细胞死亡相关。然而引人注目的是，大鼠小脑颗粒神经元和星形胶质细胞中 P2X7R 的长期激活并不影响细胞存活。 P2X7R 激活的细胞内通路涉及 MAPK、ERK1/2 和 p38 等蛋白质，与生长因子受体的相互作用可以解释它们在大鼠小脑细胞群中的行为。在这项研究中，我们着手描述 P2X7R 和 Trk 受体、EGFR（表皮生长因子受体）和 BDNFR（脑源性神经营养因子受体）调节双特异性磷酸酶 DUSP1 的细胞内机制。在小脑星形胶质细胞中，P2X7R 对 DUSP1 表达的调节取决于 ERK 和 p38 的激活。 EGFR 刺激也可以诱导 DUSP1 表达，尽管不如 P2X7R 强烈。相反，EGF 在调节颗粒神经元中的 DUSP1 方面实际上无效，在颗粒神经元中 BDNF 是 DUSP1 表达的主要调节因子，而 P2X7R 只诱导轻微的反应。事实上，BDNF 引起的 DUSP1 调节反映了转录和转录后机制之间的平衡。重要的是，当 DUSP1 表达的调节受到损害时，星形胶质细胞和神经元的活力都会受损，这表明这种磷酸酶对于维持适当的细胞结构和功能至关重要。