Purinergic Signalling最新文献

{"title":"Role of macrophage ATP metabolism disorder in SiO₂‑induced pulmonary fibrosis: a review.","authors":"Hui-Jie Hu, Yuan-Yuan Fu, Shu-Ling Du, Yu-Han Zhang, Zhao-Qiang Zhang, Gui-Zhi Han","doi":"10.1007/s11302-025-10093-8","DOIUrl":"https://doi.org/10.1007/s11302-025-10093-8","url":null,"abstract":"<p><p>Silicosis, a chronic lung disease, results from prolonged inhalation of silica dust (SiO₂) in occupational environments, and its pathogenesis remains incompletely elucidated. Studies have shown that alveolar macrophages (AMs) play a pivotal role in its development. These AMs phagocytose the inhaled SiO₂, which leads to morphological, structural, and functional abnormalities that result in lung fibrosis. During this process, adenosine triphosphate (ATP) not only provides energy for the physiological and pathological activities but also acts as a key intracellular and extracellular signaling molecule and regulates cytokine synthesis and secretion. This complex process has not been systematically summarized. In this study, first, the current data on ATP metabolism in the development of SiO₂-induced pulmonary fibrosis are introduced. ATP metabolism disorder, caused by impaired production, utilization, or distribution of ATP, disrupts macrophage energy homeostasis. Then, how ATP metabolism disorder affects macrophage morphology and function and the inflammatory and fibrotic processes of the lungs by activating the P2X7 receptor-mediated ATP signaling pathway are discussed. Finally, current therapeutic strategies targeting ATP metabolism disorder and ATP signaling pathways in silicosis are summarized. In conclusion, SiO₂-induced ATP metabolism disorder indirectly accelerates the progression of silicosis fibrosis.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144043741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expanding the P2X7R toolbox: discovery of a novel Iodine-125 radioligand.","authors":"Giorgia Tempra, Carlo Matera","doi":"10.1007/s11302-025-10094-7","DOIUrl":"https://doi.org/10.1007/s11302-025-10094-7","url":null,"abstract":"<p><p>This Journal Club article reviews a 2025 study by Qiu et al. that reports the development of a novel iodine-125 radioligand targeting the purinergic P2X7 receptor (P2X7R). The researchers created a small library of structurally modified P2X7R antagonists and identified compound 1c as a lead due to its high affinity and selectivity. Radiolabeling with iodine-125 produced [¹²⁵I]1c with high yield and purity. Binding studies confirmed its strong nanomolar affinity, supporting its use in radioligand screening and potential applications in imaging P2X7R in inflammatory and neurodegenerative diseases. The study demonstrates the value of radiolabeled probes in drug discovery and purinergic signaling research.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143976575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The P2Y₂ receptor: a new player in taste buds.","authors":"Jian-Xiong Zhou, Yong Tang","doi":"10.1007/s11302-025-10091-w","DOIUrl":"https://doi.org/10.1007/s11302-025-10091-w","url":null,"abstract":"","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144011727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"P2 receptors signaling in the esophagus: from inflammation to cancer.","authors":"Aline Zaparte, Fernanda F Cruz, Julia B de Souza, Fernanda B Morrone","doi":"10.1007/s11302-025-10089-4","DOIUrl":"https://doi.org/10.1007/s11302-025-10089-4","url":null,"abstract":"<p><p>The signaling mechanisms of nucleotides and nucleosides have been extensively studied over the past decades in various conditions affecting distinct organs and tissues. It is well-established that purinergic receptors are expressed in healthy tissues, with expression levels often increasing under pathological conditions. These receptors play crucial roles in numerous physiological and pathological processes, including inflammation, tissue repair, and cellular signaling. However, the purinergic context in the esophagus and its associated pathologies remains poorly understood, representing a significant gap in current knowledge. In this review, we compiled and analyzed the available data on the involvement of P2 purinergic receptors in esophageal diseases, such as gastroesophageal reflux disease and esophageal carcinoma. Specifically, we discuss the pharmacological modulation, functional characterization, and expression patterns of these receptors in various esophageal cell lines and immune tissue samples, under both healthy and pathological conditions. Understanding the mechanisms of action and signaling pathways involving P2 purinergic receptors in the esophagus can offer valuable insights into their biological roles and emphasize their potential as therapeutic targets for future clinical applications.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144014692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A_2A receptors: a new target for immunotherapy resistance in prostate cancer.","authors":"He-Xia Peng, Yong Tang","doi":"10.1007/s11302-025-10092-9","DOIUrl":"https://doi.org/10.1007/s11302-025-10092-9","url":null,"abstract":"","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143991820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"P2Y₆R together with CYSLTR2 serves as endogenous receptor for long-chain ceramides in atherosclerosis.","authors":"Qing Ye, Yong Tang","doi":"10.1007/s11302-025-10090-x","DOIUrl":"https://doi.org/10.1007/s11302-025-10090-x","url":null,"abstract":"<p><p>In a recent article published in Nature, 2025 Zhang et al. identified the pyrimidinergic receptor P2Y₆ (P2Y₆R), together with the cysteinyl leukotriene receptor 2 (CYSLTR2), as key receptor mediating ceramide-induced atherosclerotic cardiovascular disease (ASCVD). High levels of plasma ceramides bind to P2Y₆R and CYSLTR2, activating the Gαq signaling pathway, which triggers NLRP3 inflammasome activation and the release of the pro-inflammatory cytokine IL-1β, thereby accelerating the progression of atherosclerosis. These findings provide credible evidence supporting the long-chain ceramides as clinical predictors for risks of ASCVD. Designing small-molecule drugs and antagonists that target the binding sites of ceramide-CYSLTR2/P2Y₆R complexes presents a potential clinical strategy beyond traditional lipid-lowering therapies.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144014658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"P2Y6 promoted pruning of FSTL1 nerves by cutaneous macrophages to reset pain threshold and cardiac function.","authors":"Yun Liu, Xiao Sun, Zhengxu Jia, Qun Hou, Mingqian Yuan, Tiancheng Xu, Jinhong Yuan, Bin Xu, Zhi Yu","doi":"10.1007/s11302-025-10088-5","DOIUrl":"https://doi.org/10.1007/s11302-025-10088-5","url":null,"abstract":"<p><p>Hyperactivation of cutaneous macrophages promotes the development of chronic pain. Stimulation of nociceptive regions promotes neuroplasticity, which affects pain perception and related physiological responses. However, the specific mechanisms by which cutaneous macrophages sense and elicit nociceptive responses are unknown. Here, we exacerbated the reduction of systemic pain threshold after chronic heart failure (CHF) by silencing follistatin-like 1 (FSTL1), especially the abnormal cutaneous nociceptive sensation at PC6 acupoint, the site associated with cardiac involvement pain. The upregulation of P2Y6 and interleukin-27 expression is intimately linked to the activation of skin macrophages. Hyperactivation of P2Y6 receptor (P2Y6R) may be associated with MHC II M1⁺ macrophage polarization in PC6. Thus, P2Y6 is one of the key factors that modulate the functional polarization of skin macrophages, which may subsequently influence the expansion of the pain field. The supportive effect of CD206 M2⁺ macrophages on the cutaneous FSTL1⁺ nerves was significantly reduced. Meanwhile, FSTL1⁺ nerves in PC6 functionally interacted with calcitonin gene-related peptide (CGRP)⁺ nerves, and the overactivation of nerve growth factor (NGF) secreted by cutaneous macrophages induced CGRP⁺ neuropathological remodeling, which supported the enlargement of the pain sensory area. The activation of CGRP and P2X3 receptor (P2X3R), Na⁺/K⁺ ATPase (NKA), and P2X3R in the C8 DRG may be one of the molecular bases mediating cutaneous nociceptive transmission and affecting the function of the heart. Hyperactivation of NKA was consistent with decreased pain threshold and changes in cardiac dysfunction, and PC6 injection of an NKA inhibitor (digilanid C) was effective in ameliorating nociception and cardiac impairment. The beneficial effects of digilanid C were counteracted by FSTL1 silencing. These results indicated that P2Y6 mediates the remodeling of pain perception by skin macrophages via the action of FSTL1, while NKA inhibitors synergistically exert their therapeutic effects.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144042202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The anti-inflammatory effect of physical exercise on type 2 diabetes: the role of purinergic signaling.","authors":"Andréia Machado Cardoso, André Campos de Lima, Aline Manica, Daniela Zanini, Lucas Macedo Chaves, Samantha Nuncio Prestes, Sedinei Lopes Copatti, Michele Mainardi Pillat, Taís Vidal, Clodoaldo Antônio de Sá","doi":"10.1007/s11302-025-10087-6","DOIUrl":"https://doi.org/10.1007/s11302-025-10087-6","url":null,"abstract":"<p><p>This study investigated the effects of physical exercise (PE) on the modulation of purinergic signaling and inflammatory profiles in sedentary women with type 2 diabetes mellitus (T2DM). Over 16 weeks, participants underwent a combined aerobic and resistance training program. The intervention resulted in reduced extracellular ATP levels and decreased activity of E-NTPDase and ADA enzymes, shifting the inflammatory balance toward an anti-inflammatory profile. A significant increase in anti-inflammatory cytokines (IL-10, IL-4) and a decrease in pro-inflammatory markers (TNF-α, IFN-γ, IL-6) were observed in the T2DM group. Correlations indicated that ATP hydrolysis was inversely related to anti-inflammatory cytokines, supporting the role of PE in modulating purinergic pathways. Additionally, improvements in glycemic control, systolic blood pressure, and functional capacity highlighted the systemic benefits of exercise. These findings emphasize the therapeutic potential of PE in managing T2DM by targeting inflammation and metabolic dysregulation through purinergic modulation. Further studies should explore these mechanisms to optimize exercise-based interventions.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144036674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Involvement of purinergic signalling in the vasomotor response to hypochlorous acid in porcine coronary artery.","authors":"Ashwaq Baghdadi, William R Dunn, Vera Ralevic","doi":"10.1007/s11302-025-10086-7","DOIUrl":"https://doi.org/10.1007/s11302-025-10086-7","url":null,"abstract":"<p><p>Hypochlorous acid (HOCl) is generated by neutrophils during the innate immune response. ATP is released from cells by various stimuli and during inflammation but whether ATP is released by and participates in the response to HOCl is unclear. This study investigated vasomotor effects of HOCl on the porcine coronary artery (PCA) and the involvement of ATP and purine receptors. HOCl at 100 μM induced rapid and transient endothelium-dependent relaxation followed by slow and sustained endothelium-independent relaxation. Transient endothelium-dependent relaxation was induced by 500 μM HOCl, followed by endothelium-dependent contraction, then slow endothelium-independent relaxation. 8-(p-sulphophenyl)theophylline (8-SPT), an adenosine/P1 receptor antagonist, blocked rapid relaxation and contraction to HOCl but an A_2A receptor antagonist, ZM 241385, and an A₁ receptor antagonist, DPCPX, had no effect. Suramin, a P2 receptor antagonist (and membrane channel inhibitor), blocked rapid relaxation (at 100 μM HOCl) and contraction to HOCl. Other antagonists for P2, P2X1, P2Y1 and P2X4 receptors (PPADS, reactive blue 2, NF449, MRS2179 and BX430) did not affect HOCl responses. Relaxation to exogenous ATP was inhibited by 8-SPT but not by suramin suggesting that suramin block of HOCl responses may involve inhibition of membrane channels and endogenous ATP release. Apyrase, which hydrolyzes nucleotides, abolished responses to HOCl, ATP and unexpectedly adenosine. Neither probenecid nor carbenoxelone (connexin and pannexin channel inhibitors) blocked responses to HOCl. Luminescent ATP assay showed that HOCl elicited ATP release from cultures of human coronary artery endothelial cells. These findings advance our understanding of inflammation by showing that HOCl evokes endothelium-dependent vasorelaxation and contraction in coronary arteries which may involve P1 receptors implicating endogenous adenosine, possibly generated from rapid metabolism of ATP released by HOCl.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144029308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A new approach to psoriasis therapy: photoswitchable A₃ adenosine receptor activation.","authors":"Federica Cherchi, Elisabetta Coppi","doi":"10.1007/s11302-025-10079-6","DOIUrl":"https://doi.org/10.1007/s11302-025-10079-6","url":null,"abstract":"<p><p>This Journal Club article discusses a recent study by López-Cano and collaborators, published in Journal of the American Chemical Society (López-Cano et al. Pharmacol Res 170:105731, 2021), which introduces a pioneering therapeutic approach for psoriasis based on systemic administration of a photoswitchable adenosine A₃ receptor (A₃R) agonist, MRS7787, to counteract psoriasis-relate skin alterations by topic exposure to light. The study presents a synthesis strategy, photochemical characterization, and functional evaluation of the compound, which provides light-controlled relief from IL-23-induced psoriatic skin lesions in the mouse ear, a corroborated animal model of psoriasis. The innovation offers insights into localized, time-specific, and reversible modulation of G protein-coupled receptor (GPCR) activity and has implications for drug discovery and optopharmacology, highlighting their potential for new strategies in treating skin-related diseases.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}