Purinergic Signalling最新文献

{"title":"Editorial-Translation of purinergic drugs into therapeutic use.","authors":"Charles Kennedy","doi":"10.1007/s11302-025-10077-8","DOIUrl":"https://doi.org/10.1007/s11302-025-10077-8","url":null,"abstract":"","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143503864","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":"Ligand-directed covalent labelling of adenosine receptors.","authors":"Chloe Keduan Li, Karen Joan Gregory, Manuela Jörg","doi":"10.1007/s11302-025-10073-y","DOIUrl":"https://doi.org/10.1007/s11302-025-10073-y","url":null,"abstract":"","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143484009","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":"First evidence of Tityus confluens Borelli, 1899 (Buthidae) venom altering purine metabolism in rat blood cells.","authors":"Romário da Silva Portilho, Igor Leal Brito, Andreza Negreli Santos, Bruna Pache Moreschi, Malson Neilson de Lucena, Jeandre Augusto Otsubo Jaques","doi":"10.1007/s11302-025-10076-9","DOIUrl":"https://doi.org/10.1007/s11302-025-10076-9","url":null,"abstract":"<p><p>Purinergic signaling pathways play crucial roles in regulating hemostatic and inflammatory responses, both of which are impacted by scorpion envenomation. Scorpion venoms are complex mixtures of various toxins, such as peptides, enzymes, and nucleotides. Previous research showed that the action of scorpion toxins on the purinergic system stems from their effects on purinergic receptors. Additionally, a study identified a putative ectonucleotidase in scorpion venom. This study aimed to investigate the ability of Tityus confluens venom (10, 50, and 100 µg/mL) to metabolize adenine nucleotides and its potential effects on purinergic enzyme activity in rat platelets and lymphocytes. The effects of T. confluens venom on E-NTPDase (ATP and ADP hydrolysis), E-5'-NT (AMP hydrolysis), and E-ADA (ADO hydrolysis) activities were analyzed. The results revealed that crude venom from T. confluens exhibited ATP hydrolysis activity at all tested concentrations. In lymphocytes, ADP hydrolysis was inhibited by 100 µg/mL crude venom, whereas ADO hydrolysis was increased by all venom concentrations. In platelets, ATP hydrolysis was inhibited by 50 and 100 µg/mL crude venom, whereas AMP and ADO hydrolysis were inhibited by all concentrations. When considered collectively, the data suggested an elevation in extracellular ATP levels and a reduction in extracellular ADO. These findings are in alignment with clinical manifestations of scorpion envenomation characterized by a pro-inflammatory milieu. Furthermore, this study demonstrated the intrinsic ATPase activity of T. confluens venom and its ability to modulate E-NTPDase, E-5'-NT, and E-ADA activities in rat blood cells.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483996","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":"SCH58261 effectively prevents the reduction in excitability of striatal MSNs in mice following 20 h of sleep deprivation.","authors":"Jin Peng, Xinyu Huang, Peijie Liu, Yushi Hu, Liang Kang","doi":"10.1007/s11302-025-10072-z","DOIUrl":"https://doi.org/10.1007/s11302-025-10072-z","url":null,"abstract":"<p><p>Adenosine, a sleep-associated neuromodulator, is crucial in various physiological and pathological processes. Previous studies have demonstrated that sleep deprivation (SD) alters striatal neuronal activity. In this study, we used in vitro electrophysiological recordings to investigate the effects of 20 h of SD on the neuronal excitability of mouse dorsal striatal medium spiny neurons (MSNs). Our findings revealed that SD resulted in altered action potential (AP) discharge properties and reduced neuronal excitability compared to the control group. Importantly, these changes were partially offset by the prophylactic injection of the A2A receptor (A2AR) antagonist SCH58261. Additionally, 20 h of SD caused a decrease in the amplitude and an increase in the interval of spontaneous excitatory postsynaptic currents (sEPSCs) compared to control. However, the prophylactic injection of the A2AR antagonism shortened the sEPSC interval, while the A1 receptor (A1R) antagonist DPCPX not only shortened the interval but also further reduced the amplitude of sEPSCs. Thus, it can be concluded that SCH58261 effectively prevents the reduction in excitability of striatal MSNs in mice following 20 h of sleep deprivation, whereas DPCPX does not.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143449819","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":"A_2B adenosine receptor-triggered intracellular calcium mobilization: Cell type-dependent involvement of G_i, G_q, G_s proteins and protein kinase C.","authors":"Zhan-Guo Gao, Ray R Gao, Clayton K Meyer, Kenneth A Jacobson","doi":"10.1007/s11302-025-10070-1","DOIUrl":"10.1007/s11302-025-10070-1","url":null,"abstract":"<p><p>Activation of PLCβ enzymes by G_iβγ and G_αq/11 proteins is a common mechanism to trigger cytosolic Ca²⁺ increase. We and others reported that G_αq/11 inhibitor FR900359 (FR) can inhibit both G_αq- and, surprisingly, G_iβγ-mediated intracellular Ca²⁺ mobilization. Thus, the G_αi-G_βγ-PLCβ-Ca²⁺ signaling axis depends entirely on the presence of active G_αq, which reasonably explained FR-inhibited G_iβγ-induced Ca²⁺ release. However, the conclusion that G_iβγ signaling is controlled by G_αq derives mostly from HEK293 cells. Here we show that indeed in HEK293 cells both G_αq/11 siRNA and G_αq/11 inhibitors diminished Ca²⁺ increase triggered by native G_q-coupled P2Y₁ receptors, or by transfected G_i-coupled A₁- or G_s-coupled A_2B adenosine receptors (ARs). However, in T24 bladder cancer cells, G_i inhibitor PTX, but not G_αq/11 inhibitors, FR, YM254890 (YM) or G_q/11 siRNA, inhibited Ca²⁺ increase triggered by native A_2BAR activation. Simultaneous inactivation of G_i and G_s further suppressed A_2BAR-triggered Ca²⁺ increase in T24 cells. The G_αq/11 inhibitor YM fully and partially inhibited endogenous P2Y₁- and β₂-adrenergic receptor-induced Ca²⁺ increase in T24 cells, respectively. PKC activator PMA partially diminished A_2BAR-triggered but completely diminished β₂-adrenergic receptor-triggered Ca²⁺ increase in T24 cells. Neither β-arrestin1 nor β-arrestin2 siRNA affected A_2BAR-mediated Ca²⁺ increase. Unlike in T24 cells, YM inhibited native A_2BAR-triggered calcium mobilization in MDA-MB-231 breast cancer cells. Thus, G_αq/11 is vital for Ca²⁺ increase in some cell types, but G_iβγ-mediated Ca²⁺ signaling can be Gα_q/11-dependent or independent based on cell type and receptor activated. Besides G proteins, PKC also modulates cytosolic Ca²⁺ increase depending on cell type and receptor.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399825","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":"Cell cycle regulation by ADP and IGF-1 in cultured late developing glia progenitors of the avian retina.","authors":"Isis Moraes Ornelas, Thayane Martins Silva, Mariana Rodrigues Pereira, Guilherme Rapozeiro França, Ana Lucia Marques Ventura","doi":"10.1007/s11302-023-09982-7","DOIUrl":"10.1007/s11302-023-09982-7","url":null,"abstract":"<p><p>In the avian retina, ADP induces the proliferation of late developing glia progenitors. Here, we show that in serum-containing retinal cell cultures, ADP-induced increase in [³H]-thymidine incorporation can be prevented by the IGF-1 receptor antagonists AG1024 and I-OMe-Tyrphostin AG 538, suggesting the participation of IGF-1 in ADP-mediated progenitor proliferation. In contrast, no increase in [³H]-thymidine incorporation is observed in retinal cultures treated only with IGF-1. Under serum starvation, while no increase in cell proliferation is detected in cultures treated only with ADP or IGF-1, a significant increase in [³H]-thymidine incorporation and number of PCNA expressing cells is observed in cultures treated concomitantly with ADP plus IGF-1, suggesting that both molecules are required to induce proliferation of retinal progenitors. In serum-starved cultures, although an increase in cell viability is detected by MTT assays in IGF-1-treated cultures, no significant increase in viability of [³H]-thymidine labeled progenitors is observed, suggesting that IGF-1 may contribute to survival of postmitotic cells in culture. While only ADP increases intracellular calcium, only IGF-1 induces the phosphorylation of Akt in the retinal cultures. IGF-1 through the PI3K/Akt pathway induces a significant increase in the transcription and expression of CDK1 with a decrease in phospho-histone H3 expression that is concomitant with an increase in the expression of cyclins D1 and E and CDK2. These findings suggest that IGF-1 stimulates CDK-1 mRNA and protein expression that enable progenitors to progress through the cell cycle. However, signaling of ADP in the presence IGF-I seems to be required for DNA synthesis.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":"179-191"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11958921/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139049237","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 system in cancer stem cells.","authors":"J D Nuñez-Rios, H Ulrich, M Díaz-Muñoz, C Lameu, F G Vázquez-Cuevas","doi":"10.1007/s11302-023-09976-5","DOIUrl":"10.1007/s11302-023-09976-5","url":null,"abstract":"<p><p>Accumulating evidence supports the idea that cancer stem cells (CSCs) are those with the capacity to initiate tumors, generate phenotypical diversity, sustain growth, confer drug resistance, and orchestrate the spread of tumor cells. It is still controversial whether CSCs originate from normal stem cells residing in the tissue or cancer cells from the tumor bulk that have dedifferentiated to acquire stem-like characteristics. Although CSCs have been pointed out as key drivers in cancer, knowledge regarding their physiology is still blurry; thus, research focusing on CSCs is essential to designing novel and more effective therapeutics. The purinergic system has emerged as an important autocrine-paracrine messenger system with a prominent role at multiple levels of the tumor microenvironment, where it regulates cellular aspects of the tumors themselves and the stromal and immune systems. Recent findings have shown that purinergic signaling also participates in regulating the CSC phenotype. Here, we discuss updated information regarding CSCs in the purinergic system and present evidence supporting the idea that elements of the purinergic system expressed by this subpopulation of the tumor represent attractive pharmacological targets for proposing innovative anti-cancer therapies.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":"23-38"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11904000/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"107592133","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 signaling in liver disease: calcium signaling and induction of inflammation.","authors":"Henning Ulrich, Talita Glaser, Andrew P Thomas","doi":"10.1007/s11302-024-10044-9","DOIUrl":"10.1007/s11302-024-10044-9","url":null,"abstract":"<p><p>Purinergic signaling regulates many metabolic functions and is implicated in liver physiology and pathophysiology. Liver functionality is modulated by ionotropic P2X and metabotropic P2Y receptors, specifically P2Y1, P2Y2, and P2Y6 subtypes, which physiologically exert their influence through calcium signaling, a key second messenger controlling glucose and fat metabolism in hepatocytes. Purinergic receptors, acting through calcium signaling, play an important role in a range of liver diseases. Ionotropic P2X receptors, such as the P2X7 subtype, and certain metabotropic P2Y receptors can induce aberrant intracellular calcium transients that impact normal hepatocyte function and initiate the activation of other liver cell types, including Kupffer and stellate cells. These P2Y- and P2X-dependent intracellular calcium increases are particularly relevant in hepatic disease states, where stellate and Kupffer cells respond with innate immune reactions to challenges, such as excess fat accumulation, chronic alcohol abuse, or infections, and can eventually lead to liver fibrosis. This review explores the consequences of excessive extracellular ATP accumulation, triggering calcium influx through P2X4 and P2X7 receptors, inflammasome activation, and programmed cell death. In addition, P2Y2 receptors contribute to hepatic steatosis and insulin resistance, while inhibiting the expression of P2Y6 receptors can alleviate alcoholic liver steatosis. Adenosine receptors may also contribute to fibrosis through extracellular matrix production by fibroblasts. Thus, pharmacological modulation of P1 and P2 receptors and downstream calcium signaling may open novel therapeutic avenues.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":"69-81"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11958897/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352832","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":"Preclinical evaluation of bozepinib in bladder cancer cell lines: modulation of the NPP1 enzyme.","authors":"Álisson Coldebella da Silva, Juliete Nathali Scholl, Amanda de Fraga Dias, Augusto Ferreira Weber, Fernanda Bueno Morrone, Olga Cruz-López, Ana Conejo-García, Joaquín María Campos, Jean Sévigny, Fabrício Figueiró, Ana Maria Oliveira Battastini","doi":"10.1007/s11302-023-09975-6","DOIUrl":"10.1007/s11302-023-09975-6","url":null,"abstract":"<p><p>Bladder cancer (BC) is the most common cancer of the urinary tract. Bozepinib (BZP), a purine-derived molecule, is a potential compound for the treatment of cancer. Purinergic signaling consists of the activity of nucleosides and nucleotides present in the extracellular environment, modulating a variety of biological actions. In cancer, this signaling is mainly controlled by the enzymatic cascade involving the NTPDase/E-NPP family and ecto-5'-nucleotidase/CD73, which hydrolyze extracellular adenosine triphosphate (ATP) to adenosine (ADO). The aim of this work is to evaluate the activity of BZP in the purinergic system in BC cell lines and to compare its in vitro antitumor activity with cisplatin, a chemotherapeutic drug widely used in the treatment of BC. In this study, two different BC cell lines, grade 1 RT4 and the more aggressive grade 3 T24, were used along with a human fibroblast cell line MRC-5, a cell used to predict the selectivity index (SI). BZP shows strong antitumor activity, with notable IC₅₀ values (8.7 ± 0.9 µM for RT4; 6.7 ± 0.7 µM for T24), far from the SI for cisplatin (SI for BZP: 19.7 and 25.7 for RT4 and T24, respectively; SI for cisplatin: 1.7 for T24). BZP arrests T24 cells in the G₂/M phase of the cell cycle, inducing early apoptosis. Moreover, BZP increases ATP and ADP hydrolysis and gene/protein expression of the NPP1 enzyme in the T24 cell line. In conclusion, BZP shows superior activity compared to cisplatin against BC cell lines in vitro.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":"39-50"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11958895/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71426381","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 signaling in the battlefield of viral infections.","authors":"Nayara Carvalho-Barbosa, Julianna Dias Zeidler, Luiz Eduardo Baggio Savio, Robson Coutinho-Silva","doi":"10.1007/s11302-023-09981-8","DOIUrl":"10.1007/s11302-023-09981-8","url":null,"abstract":"<p><p>Purinergic signaling has been associated with immune defenses against pathogens such as bacteria, protozoa, fungi, and viruses, acting as a sentinel system that signals to the cells when a threat is present. This review focuses on the roles of purinergic signaling and its therapeutic potential for viral infections. In this context, the purinergic system may play potent antiviral roles by boosting interferon signaling. In other cases, though, it can contribute to a hyperinflammatory response and disease severity, resulting in poor outcomes, such as during flu and potentially COVID-19. Lastly, a third situation may occur since viruses are obligatory intracellular parasites that hijack the host cell machinery for their infection and replication. Viruses such as HIV-1 use the purinergic system to favor their infection and persistence within the host cell. Therefore, understanding the particular nuances of purinergic signaling in each viral infection may contribute to designing proper therapeutic strategies to treat viral diseases.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":"83-98"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11958901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138462306","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}