Purinergic Signalling最新文献

The enzymatic degradation of ATP to adenosine by microglial CD39 regulates neurovascular coupling and metabolic supply to the brain. 小胶质细胞CD39将ATP酶降解为腺苷调节神经血管偶联和脑代谢供应。

IF 3 4区医学

Purinergic Signalling Pub Date : 2025-06-20 DOI: 10.1007/s11302-025-10102-w

Jing Guo, Yong Tang, Peter Illes

引用次数: 0

P2X3 receptors in the paraventricular hypothalamus: a specific target for visceral pain. 室旁下丘脑中的P2X3受体：内脏疼痛的特定靶点。

IF 3 4区医学

Purinergic Signalling Pub Date : 2025-06-20 DOI: 10.1007/s11302-025-10099-2

Xiu-Min Hu, Yong Tang, Peter Illes

{"title":"P2X3 receptors in the paraventricular hypothalamus: a specific target for visceral pain.","authors":"Xiu-Min Hu, Yong Tang, Peter Illes","doi":"10.1007/s11302-025-10099-2","DOIUrl":"https://doi.org/10.1007/s11302-025-10099-2","url":null,"abstract":"In a recent article published in Neuron, Li et al. (Neuron 112(22):3734-3749.e5, 2024) accomplished a major scientific advance by reporting that ATP-sensitive P2X3 receptor-channels (P2X3Rs) in the paraventricular hypothalamus (PVH) specifically regulate visceral pain without affecting somatic pain. On the other hand, vasoactive intestinal polypeptide-sensing receptors (VIPR2) selectively process somatic pain without altering visceral pain. Function-dependent laser capture microdissection sequencing (fLCM-Seq) and immunohistochemistry demonstrated that P2X3Rs and VIPR2 have different transcriptional profiles and belong to the colorectal distension (CRD) and von Frey filament (VFF)-stimulated subgroups of PVH neurons, respectively. An anterograde tracing strategy, in which green fluorescent protein (GFP) was selectively expressed in CRD-labeled or VFF-labeled PVH neurons, showed that PVHP2X3R+ neuronal projections terminated exclusively at the ventral part of the lateral septal nucleus (LSV) while the PVHVIPR2+ neuronal projections terminated at the caudal part of the zona incerta (ZIC). The PVHP2X3R+ circuit selectively responded to visceral pain while remaining unresponsive to somatic pain. By contrast, the PVHVIPR2+ circuit selectively responded to somatic pain, while it did not react to visceral pain. Knockdown of P2X3R expression in PVH neurons enhanced the visceral pain threshold without affecting somatic nociception, and the reverse findings were true for the knockdown of the VIPR2 expressing PVH neurons. All these results provide possible new strategies based on central-targeted therapies for the future treatment of visceral and somatic pain, respectively.","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333818","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}

引用次数: 0

Acute effects of guanosine or inosine in a porcine model of hemorrhagic shock. 鸟苷或肌苷在猪失血性休克模型中的急性作用。

IF 3 4区医学

Purinergic Signalling Pub Date : 2025-06-17 DOI: 10.1007/s11302-025-10097-4

André P Schmidt, Denise A Otsuki, Gisele Hansel, Jean P Oses, Carolina D Wiener, Fernanda P Moreira, Luís V Portela, Diogo O Souza, Jose O C Auler

{"title":"Acute effects of guanosine or inosine in a porcine model of hemorrhagic shock.","authors":"André P Schmidt, Denise A Otsuki, Gisele Hansel, Jean P Oses, Carolina D Wiener, Fernanda P Moreira, Luís V Portela, Diogo O Souza, Jose O C Auler","doi":"10.1007/s11302-025-10097-4","DOIUrl":"https://doi.org/10.1007/s11302-025-10097-4","url":null,"abstract":"Hemorrhagic shock (HS) leads to systemic hypoperfusion, impaired tissue oxygenation, and multi-organ dysfunction, including central nervous system (CNS) injury. Guanosine and inosine, purine nucleosides with neuroprotective and anti-inflammatory properties, have demonstrated beneficial effects in models of neurotoxicity, ischemia, and septic shock. This study evaluated the acute effects of guanosine and inosine in fluid resuscitation, focusing on brain energy metabolism, neuroinflammatory mechanisms, and hemodynamic responses in a porcine model of HS. Thirty pigs (25-30 kg) underwent controlled hemorrhage to achieve a target mean arterial pressure (MAP) of 40 - 45 mmHg, maintained for 60 min. Animals were randomized into three resuscitation groups: Lactated Ringer's solution (LR), LR + guanosine (1 mmol/L), and LR + inosine (1 mmol/L), administered over 15 - 20 min. Hemodynamic, metabolic, and neuronal parameters were monitored for 440 min post-HS, with serial blood and cerebrospinal fluid (CSF) sampling to assess glutamate, lactate, glucose, neuron-specific enolase (NSE), and inflammatory cytokines. HS induced metabolic acidosis, increased CSF glutamate levels, and elevated proinflammatory cytokines (IL-1β, TNF-α, IFN-γ, IL-8). Guanosine and inosine reduced glutamate levels more rapidly than LR alone and attenuated IL-1β and TNF-α elevations. Inosine resuscitation improved MAP, systemic vascular resistance index (SVRI), and end-diastolic volume index (EDVI), suggesting enhanced hemodynamic stabilization. Guanosine and inosine modulated neuroinflammatory and metabolic responses in HS, reducing excitotoxicity and inflammatory cytokine release. Inosine also demonstrated hemodynamic benefits. These findings support further investigation into their therapeutic potential in shock resuscitation.","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317806","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}

引用次数: 0

State of the art indicators for imaging purinergic dynamics in vitro and in vivo. 体外和体内嘌呤能动态成像的最新技术指标。

IF 3 4区医学

Purinergic Signalling Pub Date : 2025-06-17 DOI: 10.1007/s11302-025-10095-6

Yumo Li, Liwan Zhang, Bohan Li, Yulong Li, Zhaofa Wu

引用次数: 0

Depletion of P2X4 receptor alleviates prostate cancer bone metastasis through reduced cancer cell invasiveness and enhanced cell adhesion activities. P2X4受体的缺失通过降低癌细胞侵袭性和增强细胞粘附活性来缓解前列腺癌骨转移。

IF 3 4区医学

Purinergic Signalling Pub Date : 2025-06-14 DOI: 10.1007/s11302-025-10096-5

Jiepei He, Yuhan Zhou, Hector M Arredondo Carrera, Nan Li, Alison Gartland, Ning Wang

{"title":"Depletion of P2X4 receptor alleviates prostate cancer bone metastasis through reduced cancer cell invasiveness and enhanced cell adhesion activities.","authors":"Jiepei He, Yuhan Zhou, Hector M Arredondo Carrera, Nan Li, Alison Gartland, Ning Wang","doi":"10.1007/s11302-025-10096-5","DOIUrl":"https://doi.org/10.1007/s11302-025-10096-5","url":null,"abstract":"Prostate cancer (PCa) preferentially metastasizes to bone, which remains incurable and contributes significantly to mortality and morbidity. The P2X4 receptor (P2X4R) is a receptor for ATP that is highly expressed in many cancer types including PCa and is positively associated with tumorigenesis. To understand the role of P2X4R in PCa biology, particularly in PCa bone metastasis, P2X4R (P2RX4) was knocked out in human PCa cell line PC3 cells using the CRISPR/Cas9 system. Cell proliferation, apoptosis, migration, and invasion were examined using CyQUANT, Cell Meter Caspase 3/7, scratch and transwell assays. Results showed that depleting P2X4R significantly reduced cell proliferation and invasion and increased apoptosis compared to PC3 wildtype (WT) controls in vitro. To test their metastatic potential in vivo, PC3 WT and knock-out (KO) cells were intracardiacally injected into male BALB/c immunocompromised mice. Twenty-five days post-injection, there were no detectable tumours and associated bone destruction in the tibias of mice injected with KO cells, whereas tibias of over 50% mice injected with WT cells were occupied by tumour cells, with significant bone destruction observed ex vivo using micro-CT. Furthermore, RNA-seq and bioinformatic analysis of P2X4R KO cells demonstrated links between P2X4R and PCa cell adhesion, and other key signalling such as Wnt signalling. These findings suggest that P2X4R is a potential therapeutic target for PCa metastasis, particularly bone metastasis.","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144294846","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}

引用次数: 0

ATP who you are. ATP你是谁。

IF 3 4区医学

Purinergic Signalling Pub Date : 2025-06-12 DOI: 10.1007/s11302-025-10098-3

Yong Tang, Peter Illes

引用次数: 0

Role of macrophage ATP metabolism disorder in SiO₂‑induced pulmonary fibrosis: a review. 巨噬细胞ATP代谢紊乱在二氧化硅诱导的肺纤维化中的作用

IF 3 4区医学

Purinergic Signalling Pub Date : 2025-05-13 DOI: 10.1007/s11302-025-10093-8

Hui-Jie Hu, Yuan-Yuan Fu, Shu-Ling Du, Yu-Han Zhang, Zhao-Qiang Zhang, Gui-Zhi Han

{"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":"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.","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}

引用次数: 0

Expanding the P2X7R toolbox: discovery of a novel Iodine-125 radioligand. 扩展P2X7R工具箱：发现一种新的碘-125放射性配体。

IF 3 4区医学

Purinergic Signalling Pub Date : 2025-05-09 DOI: 10.1007/s11302-025-10094-7

Giorgia Tempra, Carlo Matera

引用次数: 0

The P2Y₂ receptor: a new player in taste buds. P2Y2受体：味蕾中的新角色。

IF 3 4区医学

Purinergic Signalling Pub Date : 2025-05-08 DOI: 10.1007/s11302-025-10091-w

Jian-Xiong Zhou, Yong Tang

引用次数: 0

P2 receptors signaling in the esophagus: from inflammation to cancer. 食道P2受体信号：从炎症到癌症。

IF 3 4区医学

Purinergic Signalling Pub Date : 2025-05-08 DOI: 10.1007/s11302-025-10089-4

Aline Zaparte, Fernanda F Cruz, Julia B de Souza, Fernanda B Morrone

{"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":"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.","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}

引用次数: 0