Purinergic Signalling最新文献

{"title":"Positive allosteric modulator activity of ginsenosides is restricted to P2X7 and P2X4 receptors.","authors":"Elizabeth Allum, Leanne Stokes","doi":"10.1007/s11302-026-10162-6","DOIUrl":"10.1007/s11302-026-10162-6","url":null,"abstract":"<p><p>Positive allosteric modulators of P2X7 receptors hold promise as host-directed immune enhancers in intracellular infections. We have previously reported the use of protopanaxadiol ginsenosides as positive allosteric modulators of human, rat and mouse P2X7 receptors plus human P2X4 receptors, however, the effect of ginsenosides on other P2X receptors is unknown. Here, we screened a range of ginsenosides and related glycosides at hP2X1, hP2X2 and hP2X3 receptors expressed in HEK-293 cells utilising a membrane potential assay. Our results demonstrate the utility of the membrane potential assay across all P2X receptors and the lack of significant potentiation of ATP-induced responses at hP2X1, hP2X2 and hP2X3 receptors by ginsenosides and related glycosides. We report that S-Rg3 also acts as a positive allosteric modulator at hP2X4 receptors in addition to hP2X7 receptors. This information is important for determining the selectivity of ginsenoside positive allosteric modulators for P2X7 and P2X4.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":"22 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13198603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148006501","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":"The ATP-adenosine axis as a driver of tumor-associated macrophage reprogramming in colorectal cancer: mechanistic insights into immune evasion and therapeutic vulnerabilities.","authors":"Abdullah Faisal Albukhari","doi":"10.1007/s11302-026-10156-4","DOIUrl":"10.1007/s11302-026-10156-4","url":null,"abstract":"<p><p>Colorectal cancer progression is increasingly recognized as a process shaped not only by tumor-intrinsic genetic alterations but also by dynamic interactions within the tumor microenvironment. Tumor-associated macrophages represent a dominant immune population in colorectal tumors and exhibit remarkable functional plasticity in response to metabolic and immunological cues. Among these cues, extracellular nucleotide signaling has emerged as a critical regulator of macrophage behavior. Metabolic stress, hypoxia, and cell death within colorectal tumors promote the release of extracellular ATP, which is rapidly hydrolyzed by ectonucleotidases into adenosine. This ATP-adenosine axis functions as a molecular switch that transforms pro-inflammatory immune activation into sustained immunosuppression. This mechanistic review synthesizes current evidence delineating how dysregulated extracellular ATP metabolism and adenosine signaling reprogram tumor-associated macrophages toward immunosuppressive, tumor-supportive phenotypes in colorectal cancer. This review discusses the coordinated roles of ectonucleotidases, purinergic receptors, and hypoxia-driven signaling in shaping macrophage immunometabolic states. Particular emphasis is placed on adenosine receptor-mediated pathways that impair antigen presentation, suppress cytotoxic immune responses, and contribute to resistance against immunotherapy and chemotherapy. By integrating immunometabolism, purinergic signaling, and macrophage plasticity, this review highlights the ATP-adenosine axis as a central mechanism of immune evasion in colorectal cancer. This review further explores therapeutic strategies targeting this pathway as a means to reprogram macrophages and overcome tumor-induced immune suppression. Understanding these mechanisms may support the rational development of macrophage-centered interventions aimed at restoring effective antitumor immunity.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":"22 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13179402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147949412","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":"Purinergic modulation in Parkinson's disease: the dual role of istradefylline in motor and cognitive outcomes.","authors":"Mokhtar Rejili, Hayder M Al-Kuraishy, Ali I Al-Gareeb, Ali K Albuhadily, Majid S Jabir, Mustafa M Shokr, Gaber El-Saber Batiha","doi":"10.1007/s11302-026-10160-8","DOIUrl":"10.1007/s11302-026-10160-8","url":null,"abstract":"<p><p>Istradefylline, a selective adenosine 2A receptor (A2AR) antagonist, was approved in 2019 as an adjuvant treatment to reduce \"OFF\" periods in Parkinson's disease (PD) patients. This comprehensive review evaluates its dual impact on PD, contrasting established therapeutic benefits in motor symptom management with emerging concerns regarding cognitive safety. Istradefylline enhances dopaminergic transmission in the substantia nigra pars compacta (SNpc), significantly reducing L-DOPA-induced akinesia. Beyond motor control, it exhibits neuroprotective potential by mitigating neuroinflammation, oxidative stress, and alpha-synuclein-induced neurotoxicity. However, preclinical evidence suggests a concerning paradox: istradefylline may exacerbate cognitive decline by promoting amyloid-beta (Aβ) accumulation through the overactivity of γ-secretase and the disruption of brain-derived neurotrophic factor (BDNF) signaling pathways. Furthermore, its inhibitory effect on D-aspartate protein may trigger mitochondrial dysfunction and endoplasmic reticulum stress, potentially accelerating neurodegeneration in the SNpc. While istradefylline remains a valuable non-dopaminergic strategy for stabilizing motor fluctuations, its influence on long-term cognitive function necessitates careful clinical consideration. Understanding the molecular mechanisms behind these opposing effects is essential for optimizing its use and minimizing neurocognitive risks in PD patients. Future longitudinal trials are vital to clarify its long-term safety profile and disease-modifying potential.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":"22 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13176427/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147942891","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":"Acute effects of a single electroacupuncture session on purinergic signaling and inflammatory markers in patients with chronic nonspecific low back pain: a pilot study.","authors":"Jardel Cristiano Ecco, Vinicius Ansolin, Adinei Abadio Soares, Angela Makeli Kososki Dalagnol, Filomena Marafon, Francini Franscescon, Matheus Chimelo Bianchini, Débora Tavares de Resende E Silva","doi":"10.1007/s11302-026-10163-5","DOIUrl":"10.1007/s11302-026-10163-5","url":null,"abstract":"<p><p>Chronic nonspecific low back pain (CNLBP) is a problem faced by a significant portion of the world population. However, among the strategies for treating these patients, there are pharmacological and nonpharmacological options. However, noninvasive therapies are options that have been gaining prominence. Among them, electroacupuncture (EA) stands out, which can be used to treat this type of pain. Thus, the objective of our study is to investigate whether only one session with an EA protocol in patients with NCLBP could modulate the purinergic system and the levels of inflammatory cytokines. For this study, a total of 23 patients with CNLBP, of both sexes, were treated and underwent an EA session lasting 20 min. The EA protocol was performed with a needling depth of 5 mm at the acupoints (BL23, bilateral), (BL25, bilateral), (BL40, bilateral), (SP6, bilateral) and (GB-39, bilateral) with intermittent waves, low frequency of 2 Hz and pulse width of 10 mA. Blood samples were collected for analysis before and after the EA protocol. Our results, after only one session, showed a significant increase in AMP hydrolysis by ecto-5'-nucleotidase/CD73 enzyme (p = 0.0002), adenosine deaminase activity (p = 0.0382) and extracellular ATP levels (p = 0.0036). Furthermore, the EA protocol increased the expression of NTPDase/CD39 (p = 0.0287) and ecto-5'-nucleotidase/CD73 (p = 0.0007) after the 20-min treatment. Furthermore, regarding inflammatory markers, there was a significant decrease in INF-γ (p = 0.0192), IL-4 (p = 0.0011) and IL-6 (p = 0.0156) associated with an increase in IL-10 (p = 0.0031). Moreover, after one EA session increased of the CD73 expression and adenosine deaminase were strong negative correlated with inflammatory cytokines TNF-α and IL-6, respectively. The upregulation of the purinergic system, likely associated with an indirect increase in adenosine levels, may promote a shift toward an anti-inflammatory profile, characterized by increased anti-inflammatory interleukins and reduced pro-inflammatory cytokines. Thus, our results demonstrate that the beneficial effects associated with EA can be evidenced from its first session due to the ability of this therapy to modulate the purinergic system and directly or indirectly modify the levels of pro- and anti-inflammatory interleukins.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":"22 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13176375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147942894","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":"The long march towards testing the adenosine receptor agonism hypothesis for human cerebroprotection: The story of the A₁R/A₃R receptor agonist AST-004.","authors":"Theodore E Liston, William S Korinek, Kenneth A Jacobson, James D Lechleiter","doi":"10.1007/s11302-026-10161-7","DOIUrl":"10.1007/s11302-026-10161-7","url":null,"abstract":"<p><p>AST-004 is an adenosine A₁R/A₃R agonist and promising cerebroprotectant currently in Phase II clinical development. Clinical evaluations have been initiated in concussion, with trials in preparation for mild complicated traumatic brain injury (TBI) and acute ischemic stroke (AIS). AST-004 was discovered as the result of basic research on the P2Y₁R-activated homeostatic roles of astrocytes in cerebroprotection, including control of edema, excitotoxicity and oxidative stress. AST-004 was identified as the active nucleoside metabolite of the P2Y₁R agonist MRS2365. Subsequent research demonstrated that astrocyte mitochondrial ATP production could be activated by AST-004, resulting in significant efficacy in rodent models of permanent and transient occlusion AIS, porcine models of TBI and a non-human primate model of AIS as well as models of neurodegeneration and addiction. The purpose of this review is to highlight the research that led to the discovery of AST-004, summarize its widespread preclinical efficacy in a variety of disease models, and describe how this compound's excellent safety and pharmaceutical profile is differentiated from prototypical A₁R and A₃R agonists formerly or currently in the clinic.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":"22 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13168404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147875715","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":"The analgesic effect of electroacupuncture in alleviating paclitaxel-induced peripheral neuropathic pain and its possible mechanism relates to TLR4/P2X7-NLRP3 signaling pathway.","authors":"Yuan-Xi Zhou, Man-Ni Wang, Juan-Juan Xin, Jing-Wei Tan, Xiao Sang, Yu-Xue Zhao","doi":"10.1007/s11302-026-10158-2","DOIUrl":"10.1007/s11302-026-10158-2","url":null,"abstract":"<p><p>Paclitaxel-induced peripheral neuropathic pain (PIPNP) is a common and debilitating adverse effect of chemotherapy, with limited effective treatments. Electroacupuncture (EA) has demonstrated analgesic potential in various pain models, but its efficacy and mechanisms in PIPNP remain incompletely understood. This study aimed to evaluate the analgesic effect of EA in a murine model of PIPNP and investigate whether its mechanism involves modulation of the TLR4/P2X7-NLRP3 signaling pathway. A PIPNP model was established in male C57BL/6 J mice by intraperitoneal injection of paclitaxel (cumulative dose 8 mg/kg). Mice were randomly divided into control, PIPNP model, PIPNP with EA treatment at different intensities (0.5, 1.0, and 2.0 mA), and sham EA groups. Mechanical allodynia and thermal hyperalgesia were assessed using von Frey filaments and hot plate tests, respectively. Immunofluorescence staining and western blotting were employed to analyze the expression of pain-related neurotransmitters (substance P, CGRP, p75) and key components of the TLR4/P2X7-NLRP3 signaling pathway in plantar tissues, dorsal root ganglia (DRG), and spinal cord. EA treatment, particularly at 1.0 mA, significantly alleviated paclitaxel-induced mechanical allodynia and thermal hyperalgesia. Paclitaxel administration upregulated substance P, CGRP, and p75 in plantar tissues and activated the TLR4/P2X7-NLRP3 signaling pathway in DRG and spinal cord, as evidenced by increased expression of TLR4, P2X7, NLRP3, NF-κB, IL-1β, and IL-18. EA intervention markedly suppressed these changes, indicating its role in inhibiting neuroinflammation and modulating pain-related signaling. EA exerts analgesic effects in paclitaxel-induced neuropathic pain by attenuating the activation of the TLR4/P2X7-NLRP3 signaling pathway and reducing the expression of pain-related neurotransmitters.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":"22 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13168375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147875723","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":"The P2X4-P2X7 purinergic axis in alcohol-related liver disease: from fibrogenesis to immunotherapy resistance.","authors":"Zixuan Li, Jie Qiao, Ji Qiu","doi":"10.1007/s11302-026-10159-1","DOIUrl":"10.1007/s11302-026-10159-1","url":null,"abstract":"<p><p>Alcohol-related liver disease (ALD) is increasingly affecting younger populations globally and has become the leading cause of rising liver-related morbidity and mortality. Chronic alcohol exposure over a long period of time has been shown to result in a continuum of pathological processes including liver inflammation, fibrosis, and hepatocellular carcinoma (HCC). However, the therapeutic options for ALD are still limited due to its multifactorial morbidity mechanisms and treatment resistance. This review focuses on the critical regulatory role of the P2X4-P2X7 purinergic axis in ALD pathogenesis, and elucidates that extracellular ATP (eATP), a damage-associated molecular pattern (DAMP) released from alcohol-injured hepatocytes, activates this axis to drive ALD progression. The interaction between P2X4 and P2X7 receptors, including functional synergy and intracellular signal crosstalk, amplifies inflammatory signaling, promotes hepatic stellate cell (HSC) activation, and fosters an immunosuppressive microenvironment during fibrogenesis, ultimately leading to malignant transformation and impaired immunotherapeutic efficacy. Therefore, targeting the P2X4-P2X7 axis through selective receptor antagonism or combining antifibrotic with immunotherapeutic approaches may be a potential strategy to limit fibrosis and improve immunotherapeutic resistance. By synthesizing recent preclinical evidence, this review summarizes the pathogenic role of the P2X4-P2X7 axis in ALD and discusses the prospects of novel axis-based therapies to address unmet clinical needs in ALD management. Notably, most preclinical studies in this field lack standardized blank/sham control groups, which limits the causal inference of purinergic signaling in ALD progression.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":"22 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13157383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147864298","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":"Identification of the promoter region of the human P2RX7 gene.","authors":"Luyao Liu, Yoshiteru Kagawa, Colin L Masters, Stanley S Stylli, Theo Mantamadiotis, Ben J Gu","doi":"10.1007/s11302-026-10155-5","DOIUrl":"10.1007/s11302-026-10155-5","url":null,"abstract":"<p><p>The human P2X7 purinergic receptor is an ATP-gated ion channel expressed across a wide range of cell types, including immune, epithelial, glial, and various cancer cells. Despite its broad expression and diverse functions, little is known about the transcriptional regulation of the P2RX7 gene. In this study, the transcription initiation site of the P2RX7 gene was mapped 149/148 nucleotides upstream of the ATG start codon by using a sequencing-based primer extension method. To characterise the promoter region of the P2RX7 gene, eight DNA fragments were cloned into a dual-colour luciferase reporter vector system. The promoter activity of each fragment was assessed in transfected HEK-293 and COS-7 cells. Predicted promoter binding sequences were identified, and fluorescence-based super-electrophoretic mobility shift assay confirmed that the transcription factors YY1 and C/EBPβ directly bind to the P2RX7 promoter region.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":"22 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13157372/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147864332","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":"Increased P2X7 level does not affect anxiety or stress-coping behavior in male mice.","authors":"Lidia Urbina-Treviño, Hao Tang, Iven-Alex von Mücke-Heim, Tobias Engel, Annette Nicke, Jan M Deussing","doi":"10.1007/s11302-026-10157-3","DOIUrl":"10.1007/s11302-026-10157-3","url":null,"abstract":"<p><p>The P2RX7 gene has been linked to various neuropsychiatric disorders. In particular, the SNP rs2230912, which results in a glutamine-to-arginine substitution at position 460, has repeatedly been associated with mood disorders. Although this SNP per se does not affect receptor function, it tags a gain-of-function haplotype that has been shown to significantly enhance receptor activity. BAC-transgenic P2X7-reporter mice have proven to be valuable tools for monitoring P2X7 expression. Here, we exploited their capacity to simultaneously overexpress the receptor, thereby serving as gain-of-function models to assess the behavioral consequences of elevated P2X7 levels. We used the two currently available transgenic P2X7 reporter lines (sEGFP and P2X7-EGFP), which differ in their expression pattern, degree of overexpression, and co-expression of the neighbouring P2rx4 gene. Male sEGFP and P2X7-EGFP mice showed no alterations in general activity or in measures of anxiety-related or stress-coping behavior compared to their wild-type littermates. Only male P2X7-EGFP mice exhibited slightly delayed locomotor habituation to a novel environment. To what extent higher expression levels reflect enhanced receptor activity, as conveyed by the disease-associated gain-of-function haplotype, requires further investigation. Overall, these results indicate that P2X7 overexpression-whether at endogenous or ectopic sites, or in conjunction with P2X4-is not sufficient to substantially alter behavior of individually housed male mice under baseline conditions.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":"22 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13157380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147864300","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":"Functional role of peripheral P2X3 receptor expression in trigeminal ganglion neurons: a microarray-based evaluation of the antagonist effect of P2X3.","authors":"Mika Ishikawa, Takehiro Yajima, Kentaro Mizuta, Tadasu Sato","doi":"10.1007/s11302-026-10154-6","DOIUrl":"10.1007/s11302-026-10154-6","url":null,"abstract":"<p><p>The P2X receptor is an extracellular adenosine triphosphate (ATP)-gated ion channel that plays critical roles in cellular and developmental processes, including cell proliferation, survival, and differentiation. Specifically, P2X3 is essential for ATP to function as a neurotransmitter in the peripheral nervous system. Despite the role of P2X3 in nociception, its specific contribution to the development of the trigeminal ganglion (TG), particularly across different developmental stages, remains undetermined. Therefore, in this study, we measured P2X3 expression in the mouse TG and peripheral tissues, investigated its function in the newborn mouse with P2X3 antagonist, and evaluated its effects using a microarray analysis. We investigated the size and number of P2X3-positive neurons in the TG and the density of P2X3-positive nerve fibers in peripheral tissues of newborn and adult mice using immunohistochemical techniques. P2X3-immunoreactivity occurred in 97.9% of the sensory neurons in the TG at P0 (postnatal day 0); however, the proportion of P2X3-positive TG neurons gradually decreased over time. By adulthood, only 45.0% of sensory neurons in the TG were immunoreactive for P2X3; these neurons were predominantly small- to medium-sized. In the vibrissa, the rate of P2X3-immunoreactive peripheral nerve fibers was significantly higher at P0 than at the adult stage, with a notable decrease during maturation. Notably, administration of a P2X3 antagonist to the vibrissal pad led to reduced leptin receptor transcription in TG neurons of neonatal mice. Collectively, these findings suggest that P2X3 plays a crucial role in the development and maturation of the TG and its associated peripheral regions.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":"22 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13103190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147779596","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}