Purinergic Signalling最新文献

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Resistance exercise exerts anti-hypertensive effects and downregulates NTPDase/CD39 and ecto-5'-nucleotidase/CD73 expression in patients with chronic kidney disease undergoing hemodialysis. 抗阻运动可降低慢性肾病血液透析患者ntpase /CD39和外泌5′-核苷酸酶/CD73的表达。
IF 2.5 4区 医学
Purinergic Signalling Pub Date : 2026-01-21 DOI: 10.1007/s11302-025-10121-7
Angela Makeli Kososki Dalagnol, Francini Franscescon, Matheus Chimelo Bianchini, Josiano Guilherme Puhle, Keroli Eloiza Tessaro da Silva, Helamã Moraes Santos, Sarah Franco Vieira de Oliveira Maciel, Débora Tavares de Resende E Silva
{"title":"Resistance exercise exerts anti-hypertensive effects and downregulates NTPDase/CD39 and ecto-5'-nucleotidase/CD73 expression in patients with chronic kidney disease undergoing hemodialysis.","authors":"Angela Makeli Kososki Dalagnol, Francini Franscescon, Matheus Chimelo Bianchini, Josiano Guilherme Puhle, Keroli Eloiza Tessaro da Silva, Helamã Moraes Santos, Sarah Franco Vieira de Oliveira Maciel, Débora Tavares de Resende E Silva","doi":"10.1007/s11302-025-10121-7","DOIUrl":"10.1007/s11302-025-10121-7","url":null,"abstract":"<p><p>Chronic kidney disease (CKD) affects approximately 13.4% of the global population and significantly impacts patients' quality of life. This study aimed to investigate the effects of resistance exercise on blood pressure and purinergic signaling in patients with CKD. Here, 28 patients with CKD performed a 12-week resistance exercise protocol during hemodialysis. Blood samples were collected before and after the intervention. Biochemical analyses, for example, NTPDases, ecto-5'-nucleotidase, and adenosine deaminase, were measured in platelets. Flow cytometry was performed to investigate CD39 and CD73 expression on lymphocytes. In addition, extracellular ATP and blood pressure were analyzed. Our findings revealed that patients with CKD present high systolic blood pressure (p = 0.0002) compared to control, and resistance exercise reduces blood pressure in these patients (p = 0.007). Regarding purinergic signaling, an increase in NTPDases, ecto-5'-nucleotidase, and adenosine deaminase was observed in patients with CKD (p = 0.0001; p = 0.0001; p = 0.0001; p = 0.0007, respectively). Surprisingly, after resistance exercise, NTPDase/ATP and ecto-5'-nucleotidase decreased (p = 0.0006; p = 0.02). CD39 and CD73 expression significantly increased on lymphocytes of CKD patients compared to control (p = 0.004; p = 0.0002, respectively). After resistance exercise, CD39 and CD73 expression was downregulated. Extracellular ATP levels were decreased in CKD (p = 0.0001), and resistance exercise restored these levels. In conclusion, CKD patients present high activity and expression of CD39 and CD73 enzymes, and resistance exercise mitigated purinergic exacerbation and presents anti-hypertensive effects in patients with CKD.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":"22 1","pages":"11"},"PeriodicalIF":2.5,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12824041/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146019516","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}
引用次数: 0
Spinal P2X3 receptors blockade reverses paclitaxel-induced allodynia in rats. 脊髓P2X3受体阻断逆转大鼠紫杉醇诱导的异常性痛。
IF 2.5 4区 医学
Purinergic Signalling Pub Date : 2026-01-21 DOI: 10.1007/s11302-025-10120-8
Pedro Segura-Chama, Lucio Antonio Ramos-Chávez, Nashiely Yañez-Recendis, Francisco Pellicer, Martha León-Olea, Angélica Almanza, Francisco Mercado
{"title":"Spinal P2X<sub>3</sub> receptors blockade reverses paclitaxel-induced allodynia in rats.","authors":"Pedro Segura-Chama, Lucio Antonio Ramos-Chávez, Nashiely Yañez-Recendis, Francisco Pellicer, Martha León-Olea, Angélica Almanza, Francisco Mercado","doi":"10.1007/s11302-025-10120-8","DOIUrl":"10.1007/s11302-025-10120-8","url":null,"abstract":"<p><p>Allodynia to mechanical stimuli is one of the most prevalent symptoms in paclitaxel-treated cancer patients. Paclitaxel induces ATP release from nerve terminals; thus, peripheral primary sensory neurons can be sensitized by ATP, as a large subgroup expresses purinergic P2X<sub>2/3</sub> and P2X<sub>3</sub> receptors. In this study, we examined the role of P2X<sub>2/3</sub> and P2X<sub>3</sub> receptors in paclitaxel-treated rats with allodynia. We assessed the paw withdrawal threshold as an allodynia test on paclitaxel-treated rats and evaluated the intrathecal and systemic effects of purinergic receptor antagonists and the transient knockdown of P2X<sub>3</sub> receptor expression in male and female allodynic rats. A single dose of paclitaxel decreased the paw withdrawal threshold to mechanical stimulation in both sexes. Pharmacological blockade of spinal P2X<sub>3</sub> and P2X<sub>2/3</sub> receptors with Ro-51, TNP-ATP, and systemic suramin reversed allodynia in paclitaxel-treated rats. In addition, the transient knockdown of P2X<sub>3</sub> receptors with intrathecal siRNA administration had an antiallodynic effect that lasted until 72 h post-transfection. Paclitaxel produced an increase in the P2X<sub>3</sub> receptor expression in dorsal root ganglia but not in dorsal horn spinal cord. In conclusion, spinal P2X<sub>2/3</sub> and P2X<sub>3</sub> receptors have a significant role in allodynia to mechanical stimulation in paclitaxel-treated rats, regardless of sex. Therefore, the blockade of these receptors could be an alternative pharmacological target for alleviating sensory symptoms of paclitaxel-induced peripheral neuropathy in patients with cancer.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":"22 1","pages":"10"},"PeriodicalIF":2.5,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12824064/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146011903","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}
引用次数: 0
Integrins α3 and α6 promote Th17 cell migration by activating the purinergic receptor P2X4. 整合素α3和α6通过激活嘌呤能受体P2X4促进Th17细胞迁移。
IF 2.5 4区 医学
Purinergic Signalling Pub Date : 2026-01-20 DOI: 10.1007/s11302-025-10126-2
Chakib Hamoudi, Anahita Lashgari, Fawzi Aoudjit
{"title":"Integrins α3 and α6 promote Th17 cell migration by activating the purinergic receptor P2X4.","authors":"Chakib Hamoudi, Anahita Lashgari, Fawzi Aoudjit","doi":"10.1007/s11302-025-10126-2","DOIUrl":"10.1007/s11302-025-10126-2","url":null,"abstract":"<p><p>Interactions of effector T cells with laminins during their trafficking across basement membranes play a crucial role in the development of the adaptive immune response and inflammatory diseases. However, the mechanisms involved in this process are not fully understood. In this study, we report that human Th17 cells express and use integrins α3 and α6 to migrate in laminin 10, which is predominant in basement membranes. We showed that laminin 10 induces via integrins α3 and α6, a sustained release of ATP from the mitochondria through pannexin-1 hemichannels, and that extracellular ATP is necessary for Th17 cell migration suggesting the implication of purinergic signaling. Inhibition studies identified a major role for the ionotropic purinergic receptor P2X4 in Th17 cell migration whereas purinergic receptors P2X7 and P2Y<sub>11</sub> had no role. Along these lines, our results showed that laminin 10 induced calcium entry into Th17 cells via the P2X4 receptor. Together these results show that integrins α3 and α6 induce Th17 cell migration by activating the P2X4 receptor. Our findings uncovered a crosstalk between laminin-binding integrins and purinergic signaling in promoting human Th17 cell migration and suggest that this pathway can play an important role in the immune response.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":"22 1","pages":"8"},"PeriodicalIF":2.5,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12819906/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146011836","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}
引用次数: 0
Abnormal purinergic signaling contributes to development of renal cysts in autosomal dominant polycystic kidney disease. 异常嘌呤能信号与常染色体显性多囊肾病肾囊肿的发生有关。
IF 2.5 4区 医学
Purinergic Signalling Pub Date : 2026-01-20 DOI: 10.1007/s11302-025-10127-1
Veniamin Ivanov, Andrew Wu, Letizia Crocetti, Ze Meng, Puja Shrestha-Maskey, Tang-Dong Liao, Indra Adrianto, Gabriella Guerrini, Pablo A Ortiz, Tengis S Pavlov
{"title":"Abnormal purinergic signaling contributes to development of renal cysts in autosomal dominant polycystic kidney disease.","authors":"Veniamin Ivanov, Andrew Wu, Letizia Crocetti, Ze Meng, Puja Shrestha-Maskey, Tang-Dong Liao, Indra Adrianto, Gabriella Guerrini, Pablo A Ortiz, Tengis S Pavlov","doi":"10.1007/s11302-025-10127-1","DOIUrl":"10.1007/s11302-025-10127-1","url":null,"abstract":"<p><p>Polycystic kidney diseases (PKD) are a group of inherited nephropathies marked by the formation of fluid-filled cysts along the nephron, which cause renal failure. Bulk RNA sequencing of microdissected renal cysts from Pkd1<sup>RC/RC</sup> mice identifies 4,970 differentially expressed genes in comparison to intact collecting ducts. A poorly understood factor of cyst growth is the high ATP level in the cyst fluid, probably released by pannexin-1 hemichannels. Here, we evaluate a novel pannexin-1 inhibitor SIL14 as a potential therapeutic agent for cyst reduction and investigate proteins involved in cystogenesis, with a focus on purinergic signaling. In patch-clamp experiments, acute SIL14 application demonstrated strong, dose-dependent inhibition of Pannexin-1-dependent currents (IC<sub>50</sub> = 12.96 µM). Chronic treatment of renal collecting duct cells with 30 μM SIL14 significantly reduced cyst size in a Matrigel model of cyst formation. Notably, RNA sequencing reveals that purinergic receptors P2Y2 and P2Y4, normally expressed in collecting ducts, were downregulated, while P2X5, P2X7, P2Y6, and P2Y12 were upregulated in the cystic epithelium. Stimulation with α,βMe-ATP or Bz-ATP (P2X7 agonists) increased cyst size and pannexin-1 expression in Matrigel cultures. Our findings indicate that the transition of normal collecting ducts to cystic epithelium is accompanied by distorted purinergic signaling and propose inhibition of luminal ATP release via pannexin-1 is a potential method to limit cystogenesis.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":"22 1","pages":"9"},"PeriodicalIF":2.5,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12819920/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146011833","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}
引用次数: 0
The role and therapeutic potential of purinergic signaling pathway in metabolic syndrome-related atherosclerosis. 嘌呤能信号通路在代谢综合征相关性动脉粥样硬化中的作用和治疗潜力。
IF 2.5 4区 医学
Purinergic Signalling Pub Date : 2026-01-19 DOI: 10.1007/s11302-025-10117-3
Xiang Li, Chengxin Gong, Chengxiao Fu, Qing Xia, Yue Zhang, Yue Du, Yuting Sun, Hong Xu
{"title":"The role and therapeutic potential of purinergic signaling pathway in metabolic syndrome-related atherosclerosis.","authors":"Xiang Li, Chengxin Gong, Chengxiao Fu, Qing Xia, Yue Zhang, Yue Du, Yuting Sun, Hong Xu","doi":"10.1007/s11302-025-10117-3","DOIUrl":"10.1007/s11302-025-10117-3","url":null,"abstract":"<p><p>Metabolic syndrome (MetS) is a cluster of interrelated and co-occurring metabolic disorders, including abdominal obesity, hyperglycemia, dyslipidemia, the reduced high-density lipoprotein (HDL) cholesterol, and/or hypertension. Cardiovascular diseases are the leading causes of death and disability in metabolic syndrome. Each component of MetS is an independent risk factor for cardiovascular diseases, and the combination of these factors can increase the incidence and severity of cardiovascular diseases, such as atherosclerosis, myocardial infarction, and heart failure, with atherosclerosis being the primary cause of cardiovascular-related death in MetS. The specific pathogenic mechanism in the occurrence and development of atherosclerosis in MetS is still not fully understood. An increasing number of studies have shown that the purinergic signaling pathway plays a significant role in atherosclerosis. ATP and ADP, key signaling molecules in the purinergic signaling pathway, are not only involved in cellular energy metabolism but also activate the purinergic signaling pathway by binding to P1 and P2 purinergic receptors (P1R and P2R), regulating vascular contraction and relaxation, and inhibiting platelet aggregation. Purinergic signaling can act as both a promoter and a resistance factor in the formation of atherosclerosis, depending on the receptor subtype and downstream signaling network. This review summarizes the specific roles and mechanisms of the purinergic signaling network in MetS-related atherosclerosis and analyzes the clinical application of targeting the purinergic signaling pathway, providing a theoretical basis and innovative ideas for basic research and clinical treatment in this field.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":"22 1","pages":"7"},"PeriodicalIF":2.5,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12816476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145998889","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}
引用次数: 0
Acupuncture alleviates postoperative hemorrhoid pain by modulating the P2X7/ERK pathway. 针刺通过调节P2X7/ERK通路减轻痔术后疼痛。
IF 2.5 4区 医学
Purinergic Signalling Pub Date : 2026-01-16 DOI: 10.1007/s11302-025-10115-5
Bin Chen, Tian Wang, Jie Gao, Yan Chen, Haijing Chang, Yi Shu, Yaling Zhang, Jiahuan Li, Guozhen Ma
{"title":"Acupuncture alleviates postoperative hemorrhoid pain by modulating the P2X7/ERK pathway.","authors":"Bin Chen, Tian Wang, Jie Gao, Yan Chen, Haijing Chang, Yi Shu, Yaling Zhang, Jiahuan Li, Guozhen Ma","doi":"10.1007/s11302-025-10115-5","DOIUrl":"10.1007/s11302-025-10115-5","url":null,"abstract":"<p><p>Postoperative pain following hemorrhoid surgery is often accompanied by emotional and cognitive disturbances, complicating recovery. Acupuncture has shown promise in modulating pain and related neuroinflammatory pathways. A rat model of mixed hemorrhoid surgery was established in seventy male Sprague-Dawley rats, and randomly divided into seven groups: control, model, acupuncture, non-acupoint acupuncture, P2X7 agonist (BzATP), normal saline, and acupuncture + agonist. Behavioral assays including open field, sucrose preference, and Von Frey tests evaluated motor activity, anhedonia, and mechanical pain threshold. ELISA measured IL-6 and TNF-α levels. ATP concentration was assessed by colorimetric assay. RT-qPCR quantified P2X7 mRNA expression. Western blot and immunohistochemistry assessed P2X7 and p-ERK protein expression in dorsal root ganglia (DRG). P2X7 antagonist A-438079 was also used to validate the involvement of P2X7 in acupuncture-mediated effects. Mind-regulating and pain-relieving acupuncture significantly improved locomotion, sucrose preference, and pain threshold compared to the model group (P < 0.01), while non-acupoint and agonist treatments showed no significant benefits. Acupuncture increased ATP levels and decreased IL-6 and TNF-α levels in DRG tissues (P < 0.01). P2X7 and p-ERK expression were elevated in the model group and suppressed following acupuncture, as confirmed by qPCR, Western blot, and immunohistochemistry. The P2X7 agonist reversed many of acupuncture's beneficial effects, indicating a role of the P2X7/ERK signaling pathway. Notably, co-administration of the P2X7 selective antagonist A-438079 counteracted the detrimental effects of BzATP and restored behavioral and biochemical outcomes to acupuncture-treated levels. Mind-regulating and pain-relieving acupuncture alleviates postoperative pain and reduces depressive-like behavior and locomotor impairments in a rat model of mixed hemorrhoids, likely through suppression of peripheral P2X7/ERK signaling and inflammation. These findings highlight P2X7 as a therapeutic target in postoperative pain and underscore the translational relevance of P2X receptors.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":"22 1","pages":"6"},"PeriodicalIF":2.5,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12811187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145990147","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}
引用次数: 0
P2Y14 receptor activation and neutrophil signaling: linking inflammation to systemic pathophysiology. P2Y14受体激活和中性粒细胞信号传导:炎症与全身病理生理的联系。
IF 2.5 4区 医学
Purinergic Signalling Pub Date : 2026-01-15 DOI: 10.1007/s11302-025-10113-7
Renan da Silva Ebone, Pedro Henrique Doleski, Matheus Henrique Jantsch, Rafaella Pereira da Silveira, Daniela Bitencourt Rosa Leal
{"title":"P2Y14 receptor activation and neutrophil signaling: linking inflammation to systemic pathophysiology.","authors":"Renan da Silva Ebone, Pedro Henrique Doleski, Matheus Henrique Jantsch, Rafaella Pereira da Silveira, Daniela Bitencourt Rosa Leal","doi":"10.1007/s11302-025-10113-7","DOIUrl":"10.1007/s11302-025-10113-7","url":null,"abstract":"<p><p>Neutrophils are essential effector cells of the innate immune system, acting as the first line of defense against infection and tissue injury. Among the purinergic receptors expressed in these cells, P2Y14 has gained increasing attention in recent years for its role in modulating neutrophil recruitment and activation in inflammatory contexts. This receptor is activated mainly by uridine diphosphoglucose (UDP-glucose) and other UDP-sugars released during cellular stress or damage. Through the activation of G protein-coupled pathways, particularly via Gi/o and RhoA signaling, P2Y14 influences key neutrophil functions, including chemotaxis, cytoskeletal rearrangements, and oxidative responses. Despite its pro-inflammatory potential, and the increasing amount of literature data in recent years, P2Y14's complete physiological and pathological roles remain underexplored. Literature data also highlight its involvement in diseases like glioblastoma and COVID-19, where, due to increased neutrophil infiltration, it exacerbates inflammation, tissue damage, and stress. Therefore, targeting P2Y14 may be a promising strategy to modulate neutrophil chemotaxis and mitigate unwanted harmful inflammatory responses. This review discusses the characteristics and signaling mechanisms of P2Y14 in neutrophils, as well as the relevant implications of this pathway for neutrophil function.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":"22 1","pages":"5"},"PeriodicalIF":2.5,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12804551/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145970942","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}
引用次数: 0
Adenosine A2A receptors in the nucleus accumbens regulate stress resilience and predict susceptibility to stress-induced affective disturbances. 伏隔核中的腺苷A2A受体调节应激恢复能力并预测对应激诱导的情感障碍的易感性。
IF 2.5 4区 医学
Purinergic Signalling Pub Date : 2026-01-14 DOI: 10.1007/s11302-025-10118-2
Laura Menegatti Bevilacqua, Francisco da Silveira Neto, Axel Fogaça Rosado, Cibele Martins Pinho, Nicolle Platt, Manuella P Kaster
{"title":"Adenosine A2A receptors in the nucleus accumbens regulate stress resilience and predict susceptibility to stress-induced affective disturbances.","authors":"Laura Menegatti Bevilacqua, Francisco da Silveira Neto, Axel Fogaça Rosado, Cibele Martins Pinho, Nicolle Platt, Manuella P Kaster","doi":"10.1007/s11302-025-10118-2","DOIUrl":"10.1007/s11302-025-10118-2","url":null,"abstract":"<p><p>Individual variability in stress responses contributes to susceptibility or resilience to mood and anxiety disorders. The adenosinergic system, particularly A1 and A2A receptors, modulates synaptic activity in brain regions involved in emotional regulation, including the nucleus accumbens (NAc), a central hub of reward processing and stress responsivity. Despite high adenosine receptor expression in the NAc, their specific role in stress resilience remains poorly understood. Here, we investigated the effects of 10 days of chronic social defeat stress (CSDS) on A1 and A2A receptor expression and synaptic proteins in the NAc of male C57BL/6 mice categorized as resilient (RES) or susceptible (SS) based on their sociability. SS mice exhibited social avoidance and elevated anxiety-like behaviors, whereas RES mice behaved comparably to controls. Neurochemical analyses revealed that RES mice had lower A2A receptor mRNA levels and decreased PSD-95 expression, suggesting reduced excitatory synaptic tone, while A1 receptor and gephyrin levels remained unchanged. To assess whether baseline adenosine signaling predicts stress vulnerability, we applied a caffeine responsiveness index. Caffeine, a non-selective adenosine receptor antagonist (7.5 mg/kg, i.p.), was used to classify Swiss mice as caffeine-responsive or non-responsive based on its psychostimulant effects, which are primarily attributed to A2A receptor antagonism. Following a 14-day washout, animals were exposed to chronic variable stress (CVS), and caffeine-responsive mice showed deficits in motivational and exploratory behaviors. Together, these findings indicate that lower A2A receptor signaling in the NAc supports stress resilience, whereas heightened baseline caffeine sensitivity may predict vulnerability to stress-induced affective disturbances.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":"22 1","pages":"4"},"PeriodicalIF":2.5,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12804523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145970880","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}
引用次数: 0
Capsaicin suppresses LPS-induced inflammatory responses via NLRP3/CASP-1/IL-1β axis and purinergic pathways in BV-2 microglial cells. 辣椒素通过NLRP3/CASP-1/IL-1β轴和BV-2小胶质细胞的嘌呤能通路抑制lps诱导的炎症反应。
IF 2.5 4区 医学
Purinergic Signalling Pub Date : 2026-01-12 DOI: 10.1007/s11302-025-10123-5
Bianca Vedoin Copês Rambo, Milagros Fanny Vera Castro, Mairin Schott, Robson Lourenço da Silva Santos, Charles Elias Assmann, Marcylene Vieira da Silveira, Pâmela de Almeida Milioni, Adriel Antonio Schirmann, Vitor Bastianello Mostardeiro, Nathieli Bianchin Bottari, Maria Rosa Chitolina Schetinger, Vera Maria Melchiors Morsch
{"title":"Capsaicin suppresses LPS-induced inflammatory responses via NLRP3/CASP-1/IL-1β axis and purinergic pathways in BV-2 microglial cells.","authors":"Bianca Vedoin Copês Rambo, Milagros Fanny Vera Castro, Mairin Schott, Robson Lourenço da Silva Santos, Charles Elias Assmann, Marcylene Vieira da Silveira, Pâmela de Almeida Milioni, Adriel Antonio Schirmann, Vitor Bastianello Mostardeiro, Nathieli Bianchin Bottari, Maria Rosa Chitolina Schetinger, Vera Maria Melchiors Morsch","doi":"10.1007/s11302-025-10123-5","DOIUrl":"10.1007/s11302-025-10123-5","url":null,"abstract":"<p><p>Microglial activation drives neuroinflammation, a key factor in many neurological diseases. The purinergic system is a major regulator of inflammatory responses and represents a promising target for controlling neuroinflammation. Capsaicin, a bioactive compound found in chili peppers, exhibits significant anti-inflammatory and antioxidant properties. This study aimed to investigate the modulatory effects of capsaicin on microglial activation and purinergic system regulation. For this, BV-2 microglial cells were exposed to lipopolysaccharide (1 μg/mL) and treated with capsaicin (25 and 50 μM) for 24 hours. Cell viability was assessed by MTT and trypan blue assays. Cell cycle and apoptosis were evaluated by flow cytometry. Nitric oxide, reactive species and malondialdehyde levels were evaluated as markers of oxidative stress. Activities of NTPDase, 5'-nucleotidase (5'-NT), and adenosine deaminase (ADA) were evaluated. Gene expression of inflammatory mediators and purinergic receptors were analyzed by qRT-PCR, and molecular docking analyses were performed. As a result, capsaicin decreased the expression of pro-inflammatory mediators (NLRP3, CASP-1, IL-1β, IL-6, and TNF-α), increased IL-10 expression, and attenuated oxidative stress. It reduced NTPDase, 5'-NT, and ADA activities, downregulated P2X7 and A2A receptor expression, and upregulated A1 receptor expression. Molecular docking revealed that capsaicin has a high affinity for the A1 and A2A receptors, as well as for ADA. Collectively, these findings suggest that capsaicin exerts neuroprotective effect by suppressing pro-inflammatory signaling, enhancing anti-inflammatory responses, reducing oxidative stress, and modulating key components of the purinergic system, including ectoenzyme activities and P2X7, A1, and A2A receptor expression.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":"22 1","pages":"3"},"PeriodicalIF":2.5,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12796030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145952823","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}
引用次数: 0
2025 World congress on purines-Chengdu, China. 2025年世界嘌呤大会-中国成都。
IF 2.5 4区 医学
Purinergic Signalling Pub Date : 2026-01-07 DOI: 10.1007/s11302-025-10125-3
Peter Illes, Alexei Verkhratsky, Yong Tang
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