Nadine Linhares, Marco Aurelio Teófilo, Juliane Fernandes, Maria Jennifer Bernardino, Rachel Solidonio, Vanessa Sousa, Gisele Barreto, Everton da Silva, Ariana Maria Soares, Sthefane Feitosa, Denis Gonçalves, Delane Gondim, Renata Leitão, Mirna Marques, Paula Goes
{"title":"Blockage of P2X7 receptor activation attenuated bone loss in ligature-induced model of periodontitis in rats.","authors":"Nadine Linhares, Marco Aurelio Teófilo, Juliane Fernandes, Maria Jennifer Bernardino, Rachel Solidonio, Vanessa Sousa, Gisele Barreto, Everton da Silva, Ariana Maria Soares, Sthefane Feitosa, Denis Gonçalves, Delane Gondim, Renata Leitão, Mirna Marques, Paula Goes","doi":"10.1007/s11302-025-10112-8","DOIUrl":"https://doi.org/10.1007/s11302-025-10112-8","url":null,"abstract":"<p><p>Periodontitis is a highly prevalent immunoinflammatory disease that compromises the supporting tissues of the teeth, especially the periodontal ligament and alveolar bone. During disease progression, inflammatory responses lead to the release of ATP, which interacts with purinergic receptors such as P2X7R, potentially influencing bone remodeling. Although P2X7R has been studied in bone cells, its specific role in periodontitis remains poorly characterized. This study aimed to evaluate the effects of P2X7R modulation on osteoblastic activity and experimental bone loss. In vitro, P2X7R expression was confirmed in OFCOL II osteoblastic cells. Receptor activation using BzATP significantly reduced cell viability, altered cell morphology, and decreased alkaline phosphatase (ALP) activity (p < 0.05). In vivo, periodontitis was induced in Wistar rats via ligature. Animals were allocated into four groups: (1) Naïve; (2) Periodontitis (saline-treated); (3) BzATP-treated (P2X7R agonist); and (4) BBG-treated (P2X7R antagonist). BzATP aggravated periodontal damage, with increased inflammation, loss of osteoblasts, and disorganization of periodontal ligament fibers. In contrast, BBG improved tissue architecture, reduced inflammatory infiltrate, and increased osteoblast numbers and ALP activity, possibly via the Wnt signaling pathway. These results suggest that P2X7R activation contributes to inflammation-driven bone loss, impairing osteoblast viability and function. Therefore, P2X7R inhibition may serve as a promising pharmacological strategy to preserve bone and periodontal integrity in the context of periodontitis.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145186602","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}
Eduarda Valcarenghi Jabonski, Simone Luciana Triquez, Ana Paula Geraldi Norbah, Daiane Manica, Keroli Eloiza Tessaro da Silva, Karlla Rackell Fialho Cunha, Nagilla Moreira Cordeiro, Marcelo Moreno, Débora Tavares de Resende E Silva, Sarah Franco Vieira de Oliveira Maciel
{"title":"Breast cancer patients present pro-tumor biomarkers related to purinergic signaling and oxidative stress.","authors":"Eduarda Valcarenghi Jabonski, Simone Luciana Triquez, Ana Paula Geraldi Norbah, Daiane Manica, Keroli Eloiza Tessaro da Silva, Karlla Rackell Fialho Cunha, Nagilla Moreira Cordeiro, Marcelo Moreno, Débora Tavares de Resende E Silva, Sarah Franco Vieira de Oliveira Maciel","doi":"10.1007/s11302-025-10110-w","DOIUrl":"https://doi.org/10.1007/s11302-025-10110-w","url":null,"abstract":"<p><p>Breast cancer (BC) is a multifactorial disease characterized by cell cycle disorder and immune evasion. Studies reveal that the purinergic system (PS) is a mediator of the immune system and actively participates in the inflammatory process in cancer. Also, there is growing debate about the role of oxidative stress (OS) markers and interleukins as predictors of BC progression and invasion. Thus, PS and OS markers, in addition to the expression of interleukins and quantification of extracellular ATP, were evaluated in 39 BC patients, before the beginning of surgical or pharmacological treatment, and in 35 control participants, matched by sex and age. The results show reduced ATP and ADP hydrolysis in platelets, apart from increased extracellular ATP in the BC group. Increased AMP hydrolysis was observed in BC patients' peripheral blood mononuclear cells (PBMCs). BC patients presented elevated oxidative parameters (MDA) and reduced antioxidant parameters (SOD and ascorbic acid), and reduction in interleukins TNF, IL-4, and IL-2. In PBMC from the BC group, the expression of P2X7 gene was significantly higher in relation to the expression of CD39 gene. Also, the expression of CD39 was 1.71 fold higher in tumor samples compared to PBMC from the BC group, and it was 0.11 fold lower in PBMC from the BC group compared to the controls. We conclude that ectoenzymes that hydrolyze ATP and ADP, mainly CD39, present reduced activity in the BC group, promoting an increase in extracellular ATP and culminating in a pro-inflammatory environment, favoring cancer progression. The increase in active oxidants and the reduction in antioxidants contributed to the progression of BC in patients. Finally, TNF and IL-4 demonstrated to be promising prognostic markers in BC patients.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144966743","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":"Editorial: Purinergic signalling-a perspective from China (II).","authors":"Yong Tang, Peter Illes","doi":"10.1007/s11302-025-10111-9","DOIUrl":"https://doi.org/10.1007/s11302-025-10111-9","url":null,"abstract":"","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144966681","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 P2X7 receptor in leukemia: pathological mechanisms and therapeutic potential.","authors":"Yanwen Xue, Xiaoxiang Peng, Meng Yan, Yanan Du, Yahui Cao, Ronglan Zhao","doi":"10.1007/s11302-025-10108-4","DOIUrl":"https://doi.org/10.1007/s11302-025-10108-4","url":null,"abstract":"<p><p>The P2X7 receptor is a trimeric ion channel purinergic receptor. It plays a crucial part in the pathophysiology of cancers and a variety of inflammatory diseases and is widely expressed in different cell types. Leukemia represents a type of malignant clonal disorder that impacts the hematopoietic stem cells. Chemotherapy is one of the main treatment methods for leukemia, but there are also many side effects. In recent years, targeted therapy is a new treatment method. Research has shown that the progression and occurrence of leukemia is significantly related to the P2X7 receptor. The P2X7 receptor is also involved in the migration and invasion of leukemia cells. Furthermore, the polymorphism of the P2X7 receptor gene also takes on a significant function in the occurrence, development and clinical course of leukemia patients. The P2X7 receptor inhibitors have been found to work better in combination with existing therapeutics. Therefore, the P2X7 receptor may serve as a potential therapeutic target.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144966714","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":"Astrocytes: crucial transducers that convert norepinephrine inputs to ATP signaling in the brain.","authors":"Yuto Kubota, Eiji Shigetomi, Bijay Parajuli, Schuichi Koizumi","doi":"10.1007/s11302-025-10109-3","DOIUrl":"10.1007/s11302-025-10109-3","url":null,"abstract":"","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144874967","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":"Adenine at lower doses acts in the kidney as an aquaretic agent and prevents hyponatremia.","authors":"Alaa Alghamdi, Charuhas V Thakar, Hassane Amlal","doi":"10.1007/s11302-025-10105-7","DOIUrl":"https://doi.org/10.1007/s11302-025-10105-7","url":null,"abstract":"<p><p>We have previously reported that adenine at high doses interferes with the vasopressin signaling pathway, causes massive diuresis and volume depletion, and ultimately leads to renal failure. In the present study, we examined the effects of adenine on renal salt and water handling in a time course and dose-response study in rats housed in metabolic cages and fed control or adenine-containing diet at 1500, 2000, 2500 mg/kg and euthanized after 1, 3, and 7 weeks. Adenine at 2000 and 2500 mg/kg caused early and significant polyuria, polydipsia, and decreased urine osmolality in a dose-dependent manner without significantly affecting food intake, blood volume, blood electrolyte levels, or acid-base composition. The impaired water balance resulted from the downregulation of apical water channel AQP2 in the outer and inner medulla but not in the cortex. Adenine did not alter electrolytes (Na<sup>+</sup>, K<sup>+</sup>, Cl<sup>-</sup>) excretion at these doses for up to 3 weeks. However, a slight but significant increase in salt excretion was observed in adenine-fed rats for 7 weeks, which correlates with a significant downregulation of NKCC2, mostly in rats fed 2500 mg/kg adenine. Adenine-fed rats exhibited a substantial resistance to vasopressin in response to water deprivation or vasopressin treatment. Lastly, 2500 mg/kg adenine prevented the development of hyponatremia in a rat experimental model of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). In conclusion, adenine acts as an aquaretic agent in the kidney at lower doses and during a short feeding period. It can be used as a vasopressin antagonist in conditions associated with hyponatremia.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144822417","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":"Adenosine receptors and acute kidney injury: perspectives for future therapy.","authors":"Isabela Berton Wissmann, Renata Cristina Daniel Coelho, Lilian Baseggio, Andreia Machado Cardoso","doi":"10.1007/s11302-025-10107-5","DOIUrl":"https://doi.org/10.1007/s11302-025-10107-5","url":null,"abstract":"<p><p>Adenosine is a key modulator in the pathophysiology of acute kidney injury (AKI), particularly through its influence on inflammatory pathways and renal hemodynamics. This nucleoside exerts its effects via four G protein-coupled receptors-A1, A2A, A2B, and A3-each displaying distinct roles during renal injury. The A1 receptor primarily protects renal tissue under ischemic conditions by reducing metabolic demand, while the A2A receptor promotes anti-inflammatory and vasodilatory effects, improving renal perfusion and attenuating leukocyte infiltration. The A2B receptor, upregulated under hypoxic or injury conditions, is involved in anti-inflammatory actions and vascular integrity, especially in renal tubular and endothelial cells. Conversely, activation of the A3 receptor is generally linked to adverse outcomes, including increased apoptosis and greater tissue damage. Therapeutic strategies targeting adenosine receptors are being actively explored: selective A1 and A2A agonists show potential for promoting renal recovery, while A3 antagonists helped counteract the harmful effects of A3 activation. The review also discusses advances from recent studies (2022-2024), including insights on COVID-19-associated AKI and the nuanced roles of A1 and A3 receptors in different pathological contexts. Additionally, the therapeutic promise of inhibiting adenosine-degrading enzymes, such as ADA and adenosine kinase (ADK), is highlighted. Novel mechanistic insights and recent literature are integrated, providing a comprehensive overview that expands upon previous reviews. Although adenosine receptor modulation holds significant promise as a therapeutic strategy for AKI, further clinical research is necessary to validate efficacy and safety in human populations.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144817418","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}
Purinergic SignallingPub Date : 2025-08-01Epub Date: 2023-12-28DOI: 10.1007/s11302-023-09983-6
Wen-Jun Zhang, Li-Peng Zhang, Si-Jian Lin, Cheng-Yi Wang, Yi-Guan Le
{"title":"P2 purinergic receptors regulate the progression of colorectal cancer.","authors":"Wen-Jun Zhang, Li-Peng Zhang, Si-Jian Lin, Cheng-Yi Wang, Yi-Guan Le","doi":"10.1007/s11302-023-09983-6","DOIUrl":"10.1007/s11302-023-09983-6","url":null,"abstract":"<p><p>More and more studies have revealed that P2 purinergic receptors play a key role in the progression of colorectal cancer (CRC). P2X and P2Y purinergic receptors can be used as promoters and regulators of CRC and play a dual role in the progression of CRC. CRC microenvironment is rich in ATP and its cleavage products (ADP, AMP, Ado), which act as activators of P2X and P2Y purinergic receptors. The activation of P2X and P2Y purinergic receptors regulates the progression of CRC mainly by regulating the function of immune cells and mediating different signal pathways. In this paper, we focus on the specific mechanisms and functional roles of P2X7, P2Y12, and P2Y2 receptors in the growth and progression of CRC. The antagonistic effects of these selective antagonists of P2X purinergic receptors on the growth, invasion, and metastasis of CRC were further discussed. Moreover, different studies have reported that P2X7 receptor can be used as an effective predictor of patients with CRC. All these indicate that P2 purinergic receptors are a key regulator of CRC. Therefore, antagonizing P2 purinergic receptors may be an innovative treatment for CRC.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":"767-780"},"PeriodicalIF":2.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12454802/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139049238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Astrocytic P2X7 receptor in retrosplenial cortex drives electroacupuncture analgesia.","authors":"Wei Zhao, Si-Le Liu, Si-Si Lin, Ying Zhang, Chang Yu","doi":"10.1007/s11302-024-10043-w","DOIUrl":"10.1007/s11302-024-10043-w","url":null,"abstract":"<p><p>P2X7 receptor (P2X7R) has been found to contribute to the peripheral mechanism of acupuncture analgesia (AA). However, whether it plays an important role in central mechanism remains unknown. In this study, we aimed to reveal the role of astrocytic P2X7R in retrosplenial cortex (RSC) in AA and provide new evidence for underlying the central mechanism of AA. We applied the chemogenetic receptors hM3Dq to stimulate or hM4Di to inhibit astrocytes ligand clozapine-N-oxide (CNO) following injection of adeno-associated virus (AAV) into the bilateral RSC, or pharmacologically intervened in the activity of the purinergic receptor P2X7R. Current data indicated that chemogenetic inhibition of astrocytes or injection of P2X7R agonist Bz-ATP in the bilateral RSC significantly reverses the analgesic effect of electroacupuncture (EA) in formalin tests while the bilateral injection of the P2X7R antagonist A438079 alleviated formalin-induced nociceptive behavior. Additionally, chemogenetic suppression of astrocytic P2X7R by injection of AAV in the bilateral RSC decreased hind paw flinches induced by formalin in the mice. These findings indicate the participation of both astrocytes and P2X7R in the RSC in EA analgesic. Moreover, P2X7R on astrocytes in the RSC appears to play a critical role in the ability of EA to attenuate formalin-induced pain responses in mice.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":"523-532"},"PeriodicalIF":2.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12454730/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142111424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Purinergic SignallingPub Date : 2025-08-01Epub Date: 2025-01-18DOI: 10.1007/s11302-025-10068-9
Dan Huang, Yong Tang
{"title":"P2Y<sub>1</sub>R-IGFBP2 signaling: new contributor to astrocyte-neuron communication.","authors":"Dan Huang, Yong Tang","doi":"10.1007/s11302-025-10068-9","DOIUrl":"10.1007/s11302-025-10068-9","url":null,"abstract":"<p><p>In a recent article published in Nature Communications (Shigetomi et al Nat Commun 15(1):6525, 2024), Shigetomi et al. identified that upregulated astrocytic purinergic P2Y<sub>1</sub> receptors (P2Y<sub>1</sub>R), acting via the downstream molecule, insulin-like growth factor binding protein 2 (IGFBP2), play a crucial role in neuronal hyperexcitability. In epilepsy and stroke models, P2Y<sub>1</sub>R-IGFBP2 signaling was found to mediate astrocyte-driven neuronal hyperexcitability and so is a new contributor to astrocyte-neuron communication. Thus, IGFBP2 could be an alternative target for treating the effects of upregulated P2Y<sub>1</sub>R activity in reactive astrocytes in neurological diseases.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":"993-995"},"PeriodicalIF":2.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12454710/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143010621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}