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.

María Teresa Miras Portugal devoted most of her scientific life to the study of purinergic signalling. In an important part of her work, she used a model system: the chromaffin cells of the adrenal medulla. It was in these cells that she identified diadenosine polyphosphates, from which she proceeded to the study of adrenomedullary purinome: nucleotide synthesis and degradation, adenosine transport, nucleotide uptake into chromaffin granules, exocytotic release of nucleotides and autocrine regulation of chromaffin cell function via purinoceptors. This short review will focus on the current state of knowledge of the purinoceptors of adrenal chromaffin cells, a subject to which María Teresa made seminal contributions and which she continued to study until the end of her scientific life.

Oligodendrogliomas are diffuse low-grade gliomas of the adult central nervous system characterized by high recurrence rates and limited therapeutic options. Extracellular nucleotide signaling via purinergic receptors (P2X and P2Y) regulates pathophysiological processes in various brain tumors; however, its specific role in oligodendrogliomas remains unexplored. Here, we characterized the purinergic receptor profile in HOG cells, a human oligodendroglioma cell line, and evaluated the specific impact of P2Y₁ receptor activation on tumor cell dynamics. Single-cell calcium imaging experiments demonstrated that extracellular ATP increases intracellular calcium concentration through both extracellular influx and internal store mobilization. Expression analyses at transcript and protein levels identified ionotropic P2X4 and P2X5 receptors, alongside metabotropic P2Y₁, P2Y₂, and P2Y₄ receptors. Furthermore, the calcium responses induced by selective P2Y agonists confirmed functional responses for P2Y₁ and P2Y₂/P2Y₄ receptors. Finally, long-term time-lapse videomicroscopy combined with single-cell lineage tracking revealed that P2Y₁ activation reduced cell proliferation, prolonged cell cycle duration, tended to reduce migratory velocity, and triggered cell death. Pre-incubation with the selective P2Y₁ antagonist MRS2179 completely abrogated these effects. Taken together, our findings provide the first evidence of a functional purinergic network in HOG human oligodendroglioma cell line and highlight the P2Y₁ receptor as a tumor-suppressive candidate and potential therapeutic target for oligodendroglioma management.