Purinergic Signalling最新文献_第7页

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

IF 3 4区医学

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

Giorgia Tempra, Carlo Matera

引用次数: 0

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

IF 3 4区医学

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

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

{"title":"P2 receptors signaling in the esophagus: from inflammation to cancer.","authors":"Aline Zaparte, Fernanda F Cruz, Julia B de Souza, Fernanda B Morrone","doi":"10.1007/s11302-025-10089-4","DOIUrl":"https://doi.org/10.1007/s11302-025-10089-4","url":null,"abstract":"The signaling mechanisms of nucleotides and nucleosides have been extensively studied over the past decades in various conditions affecting distinct organs and tissues. It is well-established that purinergic receptors are expressed in healthy tissues, with expression levels often increasing under pathological conditions. These receptors play crucial roles in numerous physiological and pathological processes, including inflammation, tissue repair, and cellular signaling. However, the purinergic context in the esophagus and its associated pathologies remains poorly understood, representing a significant gap in current knowledge. In this review, we compiled and analyzed the available data on the involvement of P2 purinergic receptors in esophageal diseases, such as gastroesophageal reflux disease and esophageal carcinoma. Specifically, we discuss the pharmacological modulation, functional characterization, and expression patterns of these receptors in various esophageal cell lines and immune tissue samples, under both healthy and pathological conditions. Understanding the mechanisms of action and signaling pathways involving P2 purinergic receptors in the esophagus can offer valuable insights into their biological roles and emphasize their potential as therapeutic targets for future clinical applications.","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144014692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The anti-inflammatory effect of physical exercise on type 2 diabetes: the role of purinergic signaling. 体育锻炼对2型糖尿病的抗炎作用：嘌呤能信号的作用。

IF 3 4区医学

Purinergic Signalling Pub Date : 2025-04-16 DOI: 10.1007/s11302-025-10087-6

Andréia Machado Cardoso, André Campos de Lima, Aline Manica, Daniela Zanini, Lucas Macedo Chaves, Samantha Nuncio Prestes, Sedinei Lopes Copatti, Michele Mainardi Pillat, Taís Vidal, Clodoaldo Antônio de Sá

{"title":"The anti-inflammatory effect of physical exercise on type 2 diabetes: the role of purinergic signaling.","authors":"Andréia Machado Cardoso, André Campos de Lima, Aline Manica, Daniela Zanini, Lucas Macedo Chaves, Samantha Nuncio Prestes, Sedinei Lopes Copatti, Michele Mainardi Pillat, Taís Vidal, Clodoaldo Antônio de Sá","doi":"10.1007/s11302-025-10087-6","DOIUrl":"https://doi.org/10.1007/s11302-025-10087-6","url":null,"abstract":"This study investigated the effects of physical exercise (PE) on the modulation of purinergic signaling and inflammatory profiles in sedentary women with type 2 diabetes mellitus (T2DM). Over 16 weeks, participants underwent a combined aerobic and resistance training program. The intervention resulted in reduced extracellular ATP levels and decreased activity of E-NTPDase and ADA enzymes, shifting the inflammatory balance toward an anti-inflammatory profile. A significant increase in anti-inflammatory cytokines (IL-10, IL-4) and a decrease in pro-inflammatory markers (TNF-α, IFN-γ, IL-6) were observed in the T2DM group. Correlations indicated that ATP hydrolysis was inversely related to anti-inflammatory cytokines, supporting the role of PE in modulating purinergic pathways. Additionally, improvements in glycemic control, systolic blood pressure, and functional capacity highlighted the systemic benefits of exercise. These findings emphasize the therapeutic potential of PE in managing T2DM by targeting inflammation and metabolic dysregulation through purinergic modulation. Further studies should explore these mechanisms to optimize exercise-based interventions.","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144036674","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

Involvement of purinergic signalling in the vasomotor response to hypochlorous acid in porcine coronary artery. 猪冠状动脉对次氯酸的血管舒缩反应中嘌呤能信号的参与。

IF 3 4区医学

Purinergic Signalling Pub Date : 2025-04-16 DOI: 10.1007/s11302-025-10086-7

Ashwaq Baghdadi, William R Dunn, Vera Ralevic

{"title":"Involvement of purinergic signalling in the vasomotor response to hypochlorous acid in porcine coronary artery.","authors":"Ashwaq Baghdadi, William R Dunn, Vera Ralevic","doi":"10.1007/s11302-025-10086-7","DOIUrl":"https://doi.org/10.1007/s11302-025-10086-7","url":null,"abstract":"Hypochlorous acid (HOCl) is generated by neutrophils during the innate immune response. ATP is released from cells by various stimuli and during inflammation but whether ATP is released by and participates in the response to HOCl is unclear. This study investigated vasomotor effects of HOCl on the porcine coronary artery (PCA) and the involvement of ATP and purine receptors. HOCl at 100 μM induced rapid and transient endothelium-dependent relaxation followed by slow and sustained endothelium-independent relaxation. Transient endothelium-dependent relaxation was induced by 500 μM HOCl, followed by endothelium-dependent contraction, then slow endothelium-independent relaxation. 8-(p-sulphophenyl)theophylline (8-SPT), an adenosine/P1 receptor antagonist, blocked rapid relaxation and contraction to HOCl but an A2A receptor antagonist, ZM 241385, and an A1 receptor antagonist, DPCPX, had no effect. Suramin, a P2 receptor antagonist (and membrane channel inhibitor), blocked rapid relaxation (at 100 μM HOCl) and contraction to HOCl. Other antagonists for P2, P2X1, P2Y1 and P2X4 receptors (PPADS, reactive blue 2, NF449, MRS2179 and BX430) did not affect HOCl responses. Relaxation to exogenous ATP was inhibited by 8-SPT but not by suramin suggesting that suramin block of HOCl responses may involve inhibition of membrane channels and endogenous ATP release. Apyrase, which hydrolyzes nucleotides, abolished responses to HOCl, ATP and unexpectedly adenosine. Neither probenecid nor carbenoxelone (connexin and pannexin channel inhibitors) blocked responses to HOCl. Luminescent ATP assay showed that HOCl elicited ATP release from cultures of human coronary artery endothelial cells. These findings advance our understanding of inflammation by showing that HOCl evokes endothelium-dependent vasorelaxation and contraction in coronary arteries which may involve P1 receptors implicating endogenous adenosine, possibly generated from rapid metabolism of ATP released by HOCl.","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144029308","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

A new approach to psoriasis therapy: photoswitchable A₃ adenosine receptor activation. 一种治疗银屑病的新方法：光敏A3腺苷受体活化。

IF 3 4区医学

Purinergic Signalling Pub Date : 2025-04-07 DOI: 10.1007/s11302-025-10079-6

Federica Cherchi, Elisabetta Coppi

引用次数: 0

Rosmarinic acid modulates purinergic signaling and induces apoptosis in melanoma cells. 迷迭香酸可调节嘌呤能信号转导并诱导黑色素瘤细胞凋亡。

IF 3 4区医学

Purinergic Signalling Pub Date : 2025-04-01 Epub Date: 2024-07-20 DOI: 10.1007/s11302-024-10040-z

Gilnei B da Silva, Daiane Manica, Paula Dallagnol, Rafael A Narzetti, Filomena Marafon, Alana P da Silva, Letícia de S Matias, Joana V Cassol, Marcelo Moreno, Aniela P Kempka, Margarete D Bagatini

{"title":"Rosmarinic acid modulates purinergic signaling and induces apoptosis in melanoma cells.","authors":"Gilnei B da Silva, Daiane Manica, Paula Dallagnol, Rafael A Narzetti, Filomena Marafon, Alana P da Silva, Letícia de S Matias, Joana V Cassol, Marcelo Moreno, Aniela P Kempka, Margarete D Bagatini","doi":"10.1007/s11302-024-10040-z","DOIUrl":"10.1007/s11302-024-10040-z","url":null,"abstract":"Cancer cases have increased worldwide. Cutaneous melanoma (CM), a highly metastatic skin cancer, largely contributes to global statistical cancer death data. Research has shown that rosmarinic acid (RA) is a promising phenolic compound with antineoplastic properties. Thus, we investigated the effects of RA on apoptosis-inducing in melanoma cells, purinergic signaling modulation, and cytokine levels. We treated SK-MEL-28 cells for 24 h with different concentrations of RA and assessed the apoptosis, CD39, CD73, and A2A expression, and cytokine levels. We found RA-induced apoptosis in melanoma cells. Regarding the purinergic system, we verified that RA downregulated the expression of CD73 and A2A, specially at high concentrations of treatment. Additionally, RA increased IL-6, IL-4, IL-10, IFN-γ, and TNF-α levels. Our in vitro results confirm RA's potential to be used to induce melanoma cell apoptosis, having CD73 and A2A as targets when reversion of immune suppression is desired. Further studies in animal models and clinical trials focusing on RA's modulation of purinergic signaling in melanoma are required.","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":"353-363"},"PeriodicalIF":3.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12061826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141731338","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

Editorial-Translation of purinergic drugs into therapeutic use. 编辑-嘌呤能药物转化为治疗用途。

IF 2.4 4区医学

Purinergic Signalling Pub Date : 2025-04-01 DOI: 10.1007/s11302-025-10077-8

Charles Kennedy

引用次数: 0

Exploring novel dilazep derivatives as hENT1 inhibitors and potentially covalent molecular tools. 探索新型地拉西泮衍生物作为 hENT1 抑制剂和潜在的共价分子工具。

IF 3 4区医学

Purinergic Signalling Pub Date : 2025-04-01 Epub Date: 2024-06-15 DOI: 10.1007/s11302-024-10026-x

Majlen A Dilweg, Marina Gorostiola González, Martijn D de Ruiter, Nadine J Meijboom, Jacobus P D van Veldhoven, Rongfang Liu, Willem Jespers, Gerard J P van Westen, Laura H Heitman, Adriaan P IJzerman, Daan van der Es

{"title":"Exploring novel dilazep derivatives as hENT1 inhibitors and potentially covalent molecular tools.","authors":"Majlen A Dilweg, Marina Gorostiola González, Martijn D de Ruiter, Nadine J Meijboom, Jacobus P D van Veldhoven, Rongfang Liu, Willem Jespers, Gerard J P van Westen, Laura H Heitman, Adriaan P IJzerman, Daan van der Es","doi":"10.1007/s11302-024-10026-x","DOIUrl":"10.1007/s11302-024-10026-x","url":null,"abstract":"The human equilibrative nucleoside transporter 1 (SLC29A1, hENT1) is a solute carrier that modulates the passive transport of nucleosides and nucleobases, such as adenosine. This nucleoside regulates various physiological processes, such as vasodilation and -constriction, neurotransmission and immune defense. Marketed drugs such as dilazep and dipyridamole have proven useful in cardiovascular afflictions, but the application of hENT1 inhibitors can be beneficial in a number of other diseases. In this study, 39 derivatives of dilazep's close analogue ST7092 were designed, synthesized and subsequently assessed using [3H]NBTI displacement assays and molecular docking. Different substitution patterns of the trimethoxy benzoates of ST7092 reduced interactions within the binding pocket, resulting in diminished hENT1 affinity. Conversely, [3H]NBTI displacement by potentially covalent compounds 14b, 14c, and 14d resulted in high affinities (Ki values between 1.1 and 17.5 nM) for the transporter, primarily by the ability of accommodating the inhibitors in various ways in the binding pocket. However, any indication of covalent binding with amino acid residue C439 remained absent, conceivably as a result of decreased nucleophilic residue reactivity. In conclusion, this research introduces novel dilazep derivatives that are active as hENT1 inhibitors, along with the first high affinity dilazep derivatives equipped with an electrophilic warhead. These findings will aid the rational and structure-based development of novel hENT1 inhibitors and pharmacological tools to study hENT1's function, binding mechanisms, and its relevance in (patho)physiological conditions.","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":"289-316"},"PeriodicalIF":3.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12061832/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141327731","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

ENTPD1 (CD39) and NT5E (CD73) expression in human medulloblastoma: an in silico analysis. ENTPD1（CD39）和NT5E（CD73）在人髓母细胞瘤中的表达：硅分析。

IF 3 4区医学

Purinergic Signalling Pub Date : 2025-04-01 Epub Date: 2024-07-08 DOI: 10.1007/s11302-024-10035-w

Marco Antônio Stefani, Elizandra Braganhol, Guilherme Tomasi Santos, Samuel Masao Suwa, Daiane Dias Cabeleira, Guilherme Pamplona Bueno de Andrade

{"title":"ENTPD1 (CD39) and NT5E (CD73) expression in human medulloblastoma: an in silico analysis.","authors":"Marco Antônio Stefani, Elizandra Braganhol, Guilherme Tomasi Santos, Samuel Masao Suwa, Daiane Dias Cabeleira, Guilherme Pamplona Bueno de Andrade","doi":"10.1007/s11302-024-10035-w","DOIUrl":"10.1007/s11302-024-10035-w","url":null,"abstract":"Medulloblastoma is the most common malignant tumor in the pediatric population. Its classification has incorporated key molecular variations alongside histological characterization. CD39 (also known as ENTPD1) and CD73 (also known as NT5E), enzymes of the purinergic signaling pathway, act in synergy to generate extracellular adenosine, creating an immunosuppressive tumor microenvironment. Our study examined the expression of mRNA of these genes in previously described transcriptome data sets of medulloblastoma patient samples from the Cavalli Cohort (n = 763). Survival distribution was estimated according to the Kaplan-Meier method using a median cut-off and log-rank statistics (p ≤ 0.05). In non-WNT and non-SHH medulloblastoma Group 4 (n = 264), the high expression of ENTPD1 and NT5E was significantly related to a lower overall survival (p = 2.7e-04; p = 2.6e-03). In the SHH-activated group (n = 172), the high expression of ENTPD1 was significantly related to lower overall survival (p = 7.8e-03), while the high expression of NT5E was significantly related to greater overall survival (p = 0.017). In the WNT group (n = 63), the expressions of ENTPD1 and NT5E were not significantly correlated with overall survival (p = 0.212; p = 0.101). In non-WNT and non-SHH medulloblastoma Group 3 (n = 113), the high expression of ENTPD1 was significantly related to greater survival (p = 0.034), while expression of NT5E was not significantly related to survival of patients (p = 0.124). This in silico analysis indicates that ENTPD1 (CD39) and NT5E (CD73) can be seen as potential prognostic markers and therapeutic targets for primary medulloblastomas in non-WNT and non-SHH Group 4.","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":"331-337"},"PeriodicalIF":3.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12061802/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555371","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

Honouring Geoff Burnstock. 向杰夫-伯恩斯托克致敬

IF 3 4区医学

Purinergic Signalling Pub Date : 2025-04-01 Epub Date: 2024-11-05 DOI: 10.1007/s11302-024-10061-8

Yong Tang, Peter Illes, Charles Kennedy

引用次数: 0