Purinergic Signalling最新文献

The role of purinergic P2X3 receptors and endometriosis-associated hyperalgesia. 嘌呤能P2X3受体在子宫内膜异位症相关痛觉过敏中的作用。

IF 3 4区医学

Purinergic Signalling Pub Date : 2025-07-04 DOI: 10.1007/s11302-025-10101-x

Kailane Paula Pretto, Letícia de Souza Matias, Bruna Dias de Oliveira, Adinei Abadio Soares, Camila Ferreira Puntel, Yghor Augusto da Rocha Ricardo, Yenidis Teilor Scheibel, Débora Tavares de Resende E Silva

{"title":"The role of purinergic P2X3 receptors and endometriosis-associated hyperalgesia.","authors":"Kailane Paula Pretto, Letícia de Souza Matias, Bruna Dias de Oliveira, Adinei Abadio Soares, Camila Ferreira Puntel, Yghor Augusto da Rocha Ricardo, Yenidis Teilor Scheibel, Débora Tavares de Resende E Silva","doi":"10.1007/s11302-025-10101-x","DOIUrl":"https://doi.org/10.1007/s11302-025-10101-x","url":null,"abstract":"Endometriosis is a chronic gynecological condition characterized by endometrial tissue outside the uterine cavity. Recent research has focused on the relationship between the purinergic system and endometriosis. As a purinergic system component, extracellular adenosine triphosphate (ATP) has been involved as a crucial mediator of chronic pain associated with the disease, as well as P2X3 receptors, which play a key role in sensitization of nerve fibers and generation of nociceptive, neuropathic, and inflammatory pain. In addition, ectonucleotidases such as CD39 and CD73, which regulate ATP hydrolysis, have an altered expression in endometriotic lesions, contributing to extracellular ATP accumulation, intensifying inflammation and pain. Together, immune cells and their product are increased in endometriotic foci and promote the emergence of new lesions through their contribution to retrograde menstruation. Some studies have observed significant changes in mitochondrial respiration, notably decreased oxygen consumption in the affected endometrium. These various cellular processes that are mediated by ATP and adenosine in the uterine cavity and exert effects on immune defense will be herein reviewed in detail to investigate possible inhibitors, their activity, and potential exploration of the purinergic pathway as a therapeutic alternative.","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560967","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

Therapeutic potential of P2X7 receptor in retinal diseases. P2X7受体在视网膜疾病中的治疗潜力。

IF 3 4区医学

Purinergic Signalling Pub Date : 2025-07-04 DOI: 10.1007/s11302-025-10104-8

Min Wen, Qin Xu, Jinfeng Xie, Rong Wu, Xiaomei Chen, Nianlian Wen, Sheng Huang

{"title":"Therapeutic potential of P2X7 receptor in retinal diseases.","authors":"Min Wen, Qin Xu, Jinfeng Xie, Rong Wu, Xiaomei Chen, Nianlian Wen, Sheng Huang","doi":"10.1007/s11302-025-10104-8","DOIUrl":"https://doi.org/10.1007/s11302-025-10104-8","url":null,"abstract":"Retinal diseases affect the health of millions of people worldwide and activated P2X7 receptors (P2X7Rs) are associated with the pathophysiology of a variety of retina-related diseases, including diabetic retinopathy, age-related macular degeneration, and glaucoma. Increasing evidence indicated that P2X7R is over-activated in retinopathy and is involved in the occurrence and development of diabetic retinopathy. Purine vasotoxicity caused by over-activation of P2X7R can lead to decreased retinal blood flow and vascular dysfunction and activation of P2X7R can lead to the production of a large number of inflammatory factors, causing local inflammatory cells to infiltrate and form a vascular microenvironment, thus constituting the pathophysiological basis for the occurrence and development of retinopathy. A variety of P2X7R antagonists have been studied in clinical trials as potential treatments for retinal diseases. However, currently no P2X7R antagonists has been approved for retina diseases. In this review, we mainly focus on recent progress on the involvement of P2X7R in retinal diseases and its therapeutic potential in the future.","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560968","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

The CALHM1 blocker CGP37157 increases seizure severity during status epilepticus in adult mice. CALHM1阻滞剂CGP37157增加成年小鼠癫痫持续状态期间癫痫发作的严重程度。

IF 3 4区医学

Purinergic Signalling Pub Date : 2025-07-02 DOI: 10.1007/s11302-025-10103-9

Meghma Mitra, Amaya Sanz Rodriguez, Norman Delanty, Alan Beausang, Francesca M Brett, Michael A Farrell, Jane Cryan, Donncha F O'Brien, David Henshall, Maria F Cano-Abad, Tobias Engel

{"title":"The CALHM1 blocker CGP37157 increases seizure severity during status epilepticus in adult mice.","authors":"Meghma Mitra, Amaya Sanz Rodriguez, Norman Delanty, Alan Beausang, Francesca M Brett, Michael A Farrell, Jane Cryan, Donncha F O'Brien, David Henshall, Maria F Cano-Abad, Tobias Engel","doi":"10.1007/s11302-025-10103-9","DOIUrl":"https://doi.org/10.1007/s11302-025-10103-9","url":null,"abstract":"Epilepsy is one of the most common chronic brain diseases affecting up to 70 million people worldwide. Major challenges of epilepsy treatment include the high pharmacoresistance in patients and the lack of disease-modification. Extracellular adenosine 3'triphosphate (ATP), a key neurotransmitter in the activation of the purinergic signalling system, is increasingly recognized to contribute to pathological brain hyperexcitability in epilepsy. Consequently, targeting ATP-release mechanisms may constitute a new therapeutic strategy for seizure control and epilepsy. The calcium channel, Calcium Homeostasis Modulator 1 (CALHM1), a voltage-gated, non-selective ion channel that permits the passage of various cations and small molecules, is expressed in neurons and plays an essential role during neuronal excitability and neurotransmission. In addition to ions, CALHM1 also allows the passage of ATP into the extracellular space, activating thereby purinergic receptors. Here, we tested if the pharmacological blocking of CALHM1 via CGP37157 (7-chloro-5-(2-chlorophenyl)-3,5-dihydro-4,1-benzothiazepin-2-(1H)-one) alters the severity of intra-amygdala kainic acid-induced status epilepticus. Our results show that CGP37157 increased the severity of seizures during status epilepticus. In addition, CALHM1 protein levels are down-regulated in the hippocampus in epileptic mice and Temporal Lobe Epilepsy (TLE) patients. In summary, our results identify CALHM1 as a new contributor to seizures and suggest targeting of CALHM1 as new treatment strategy for epilepsy.","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144542056","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

Electroacupuncture alleviates capsaicin-induced rectal visceral pain in rats via inhibiting TRPV1 expression by blocking the P2X4R-activated p38 pathway. 电针通过阻断p2x4r激活的p38通路，抑制TRPV1的表达，减轻辣椒素诱导的大鼠直肠内脏疼痛。

IF 3 4区医学

Purinergic Signalling Pub Date : 2025-06-25 DOI: 10.1007/s11302-025-10100-y

Yahong Xue, Qinbing Zhu, Jing Zhang, Xiaofeng Wang

{"title":"Electroacupuncture alleviates capsaicin-induced rectal visceral pain in rats via inhibiting TRPV1 expression by blocking the P2X4R-activated p38 pathway.","authors":"Yahong Xue, Qinbing Zhu, Jing Zhang, Xiaofeng Wang","doi":"10.1007/s11302-025-10100-y","DOIUrl":"https://doi.org/10.1007/s11302-025-10100-y","url":null,"abstract":"Electroacupuncture (EA), as a combination of traditional acupuncture and modern electrotherapy, and has analgesic effects on various acute and chronic pain. It has been proved to ameliorate chronic visceral pain, but its specific role in rectal visceral pain remains underexplored. A capsaicin (CAP)-induced visceral pain rat model was established, and behavioral pain responses were observed and recorded. Measurement of mechanical pain threshold was performed using electronic Von Frey system. Rectal tissues, and the activity of microglia cells were detected by Hematoxylin/eosin staining and immunofluorescence, respectively. Contents of interleukin (IL)-6, IL-1β and tumor necrosis factor-α (TNF-α) were determined by enzyme-linked immunosorbent assay. Western blot was performed to determine the expressions of P2X4 receptor (P2X4R), p38 mitogen-activated protein kinase (p38), phosphorylated p38 (p-p38), transient receptor potential vanilloid-1 (TRPV1) and ionized calcium binding adapter molecule 1 (Iba-1). Transfection efficiency of TRPV1 overexpression plasmids was examined by quantitative real-time polymerase chain reaction. EA abrogated CAP-induced upregulation of behavioral pain responses and mechanical threshold, damage on rectal tissue, activation of microglia, stimulation of inflammatory response and promotion of P2X4R-p38-TRPV1 pathway expressions in rats, while P2X4R activation reversed the effect of EA. P2X4R antagonist weakened CAP-induced upregulation of P2X4R-p38-TRPV1 pathway expressions, microglia activation as well as increase of IL-1β in HMO6 cells, which was reversed by TRPV1 overexpression. Collectively, EA improves CAP-induced rectal visceral pain via inhibiting TRPV1 expression by blocking the P2X4R-activated p38 pathway in microglia. However, the specificity role of P2X4R needs to be confirmed by more experiment.","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485742","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

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":"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