Purinergic Signalling最新文献_第2页

Antagonism of the ATP-gated P2X7 receptor inhibits the proliferation of hepatocellular carcinoma cells. 拮抗 ATP 门控 P2X7 受体可抑制肝癌细胞的增殖。

IF 3 4区医学

Purinergic Signalling Pub Date : 2024-11-16 DOI: 10.1007/s11302-024-10064-5

Xinxing Tantai, Xin Yang, Xinyuan Liu, Xiao Yang

{"title":"Antagonism of the ATP-gated P2X7 receptor inhibits the proliferation of hepatocellular carcinoma cells.","authors":"Xinxing Tantai, Xin Yang, Xinyuan Liu, Xiao Yang","doi":"10.1007/s11302-024-10064-5","DOIUrl":"https://doi.org/10.1007/s11302-024-10064-5","url":null,"abstract":"The P2X7 receptor, an ATP-gated ion channel which belongs to the P2X receptor family, plays critical roles in recognizing extracellular adenosine 5'-triphosphate (ATP) and is widely expressed in most tumor cells as well as inflammatory cells. Previously, the P2X7 receptor has been demonstrated to modulate the progression of various malignancies, including glioblastoma, pancreatic cancer, lung cancer, leukemia, and lymphoma. However, the biological function and prognostic values of P2X7 receptor in hepatocellular carcinoma remain to be determined. Here, we investigated the expression level of P2X7 receptor in patients with hepatocellular carcinoma. Then MTS and EdU assays were carried out to study the role of P2X7 receptor blockade in the proliferation of hepatocellular carcinoma cells. In addition, the underlying mechanism was further elucidated by bulk RNAseq. Compared to the control group, the P2X7 receptor was significantly up-regulated in the hepatocellular carcinoma group. Interestingly, A740003 and A438079, two selective antagonists at P2X7 receptor, significantly blocked Ca2+ influx and decreased the proliferative rate of hepatocellular carcinoma cells. Furthermore, the expression level of chondroitin sulfate synthase 1 (CHSY1), an enzyme that mediates the polymerization step of chondroitin sulfate, was reduced by both A740003 and A438079. In conclusion, inhibition of the P2X7 receptor attenuated the proliferation of hepatocellular carcinoma cells, and this process was largely modulated by CHSY1. Thus, our findings reveal a previously unknown role for P2X7 receptor in the proliferation of hepatocellular carcinoma cells and imply that the P2X7 receptor may represent a new target for the treatment of hepatocellular carcinoma.","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644663","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

CD39 activities in the treated acupoints contributed to the analgesic mechanism of acupuncture on arthritis rats. 治疗穴位中的 CD39 活性有助于针灸对关节炎大鼠的镇痛机制。

IF 3 4区医学

Purinergic Signalling Pub Date : 2024-11-15 DOI: 10.1007/s11302-024-10065-4

Yu-Jia Li, Jie Lin, Si-Qi Tang, Wei-Min Zuo, Guang-Hong Ding, Xue-Yong Shen, Li-Na Wang

{"title":"CD39 activities in the treated acupoints contributed to the analgesic mechanism of acupuncture on arthritis rats.","authors":"Yu-Jia Li, Jie Lin, Si-Qi Tang, Wei-Min Zuo, Guang-Hong Ding, Xue-Yong Shen, Li-Na Wang","doi":"10.1007/s11302-024-10065-4","DOIUrl":"10.1007/s11302-024-10065-4","url":null,"abstract":"Our previous work had identified that at the acupuncture point (acupoint), acupuncture-induced ATP release was a pivotal event in the initiation of analgesia. We aimed to further elucidate the degradation of ATP by CD39. Acupuncture was administered at Zusanli acupoint on arthritis rats, and pain thresholds of the hindpaws were determined. Pharmacological tools or adeno-associated viruses were administered at the acupoints to interfere with targeting signals. Protein expression was determined with qRT-PCR, WB, or immunofluorescent labeling. Cultured keratinocytes, HaCaT line, were subjected to hypotonic shock to simulate needling stimulation. Extracellular ATP and adenosine levels were quantified using luciferase-luciferin assay and ELISA, respectively. Acupuncture-induced prompt analgesia was impaired by inhibiting CD39 activities to prevent the degradation of ATP to AMP but was mimicked by using CD39 agonists. Acupuncture-induced ATP accumulation exhibited synchronous changes. Similarly, acupuncture analgesia was hindered by suppressing CD73 to prevent the conversion of AMP to adenosine. Furthermore, the acupuncture effect was replicated by agonism at P2Y2Rs but inhibited by antagonism at them. Acupuncture upregulated CD73 and P2Y2Rs but not CD39. Immunofluorescent labeling demonstrated that keratinocytes were a primary site for these proteins. Shallow acupuncture also demonstrated antinociception. In vitro tests showed that hypotonic shock induced HaCaT cells to release ATP and adenosine, which was impaired by suppressing CD39 and CD73, respectively. Finally, agonism at P2Y2Rs promoted ATP release and [Ca2+]i rise. CD39 at the acupoints contributes to the analgesic mechanism of acupuncture. It may facilitate adenosine signaling in conjunction with CD73 or provide an appropriate ATP milieu for P2Y2Rs. Skin tissue may be one of the scenes for these signalings.","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142627102","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

Mechanosensitive release of ATP in the urinary bladder mucosa. 膀胱粘膜对 ATP 的机械敏感性释放。

IF 3 4区医学

Purinergic Signalling Pub Date : 2024-11-14 DOI: 10.1007/s11302-024-10063-6

Violeta N Mutafova-Yambolieva

{"title":"Mechanosensitive release of ATP in the urinary bladder mucosa.","authors":"Violeta N Mutafova-Yambolieva","doi":"10.1007/s11302-024-10063-6","DOIUrl":"10.1007/s11302-024-10063-6","url":null,"abstract":"The urinary bladder mucosa (urothelium and suburothelium/lamina propria) functions as a barrier between the content of the urine and the underlying bladder tissue. The bladder mucosa is also a mechanosensitive tissue that releases signaling molecules that affect functions of cells in the bladder wall interconnecting the mucosa with the detrusor muscle and the CNS. Adenosine 5'-triphosphate (ATP) is a primary mechanotransduction signal that is released from cells in the bladder mucosa in response to bladder wall distention and activates cell membrane-localized P2X and P2Y purine receptors on urothelial cells, sensory and efferent neurons, interstitial cells, and detrusor smooth muscle cells. The amounts of ATP at active receptor sites depend significantly on the amounts of extracellularly released ATP. Spontaneous and distention-induced release of ATP appear to be under differential control. This review is focused on mechanisms underlying urothelial release of ATP in response to mechanical stimulation. First, we present a brief overview of studies that report mechanosensitive ATP release in bladder cells or tissues. Then, we discuss experimental evidence for mechanosensitive release of urothelial ATP by vesicular and non-vesicular mechanisms and roles of the stretch-activated channels PIEZO channels, transient receptor potential vanilloid type 4, and pannexin 1. This is followed by brief discussion of possible involvement of calcium homeostasis modulator 1, acid-sensing channels, and connexins in the release of urothelial ATP. We conclude with brief discussion of limitations of current research and of needs for further studies to increase our understanding of mechanotransduction in the bladder wall and of purinergic regulation of bladder function.","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142627103","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

Electroacupuncture may alleviate inflammatory pain by downregulating the expression of P2Y₁₄ receptor in the primary somatosensory cortex. 电针可通过下调初级躯体感觉皮层中 P2Y14 受体的表达来缓解炎性疼痛。

IF 3 4区医学

Purinergic Signalling Pub Date : 2024-11-07 DOI: 10.1007/s11302-024-10058-3

Shuai Hou, Cui-Yuan Chen, Rui-Zhu Zhou, Liu-Xuan He, Xiao-Xiao Zhao, Sha-Sha Chen, Sha Yang, Hai-Yan Yin, Shu-Guang Yu

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 : 2024-11-05 DOI: 10.1007/s11302-024-10061-8

Yong Tang, Peter Illes, Charles Kennedy

引用次数: 0

The exploration of active components of 701 Dieda Zhentong patch and analgesic properties on chronic constriction injury rats. 701地达镇痛贴有效成分及对慢性收缩性损伤大鼠镇痛作用的探讨

IF 3 4区医学

Purinergic Signalling Pub Date : 2024-11-04 DOI: 10.1007/s11302-024-10056-5

Jun Meng, Zhenglang Zhang, Yujie Wang, Lina Long, Anqi Luo, Zhenhui Luo, Kexin Cai, Xi Chen, Hong Nie

{"title":"The exploration of active components of 701 Dieda Zhentong patch and analgesic properties on chronic constriction injury rats.","authors":"Jun Meng, Zhenglang Zhang, Yujie Wang, Lina Long, Anqi Luo, Zhenhui Luo, Kexin Cai, Xi Chen, Hong Nie","doi":"10.1007/s11302-024-10056-5","DOIUrl":"https://doi.org/10.1007/s11302-024-10056-5","url":null,"abstract":"An increasing number of traditional Chinese medicine(TCM) have been confirmed to possess analgesic bioactivity. 701 Dieda Zhentong patch(701-DZP) which includes 14 kinds of TCMs exhibited excellent efficacy in alleviating back or leg pain after a soft-tissue injury. In this study, UPLC/MS was used to construct the fingerprint of 701-DZP and excavate the potential bioactive ingredients of it. 21 compounds were detected and identified in the fingerprint including 12 compounds that pass through the skin and 6 compounds observed in the plasma. Then, the role of 701-DZP in neuropathic pain(NPP) was assessed by network pharmacology and CCI rats. 701-DZP inhibited pain sensitization(MWT and TWL) and the release of inflammation mediators(IL-1β and IL-6) in CCI rats which were in keeping with the core targets of the PPI network. The results of IHC and Western blot showed that the expression of the P2X3 receptor in the DRG and SC of CCI rats was significantly reduced after the treatment with 701-DZP. Moreover, the 701-DZP down-regulated the level of phosphorylation of ERK1/2 MAPK instead of P38 MAPK in the DRG of CCI rats. In conclusion, this study has clarified 6 potential analgesic active compounds of 701-DZP and explored the analgesic properties, which may inhibit the expression of the P2X3 receptor to reduce the release of inflammatory mediators based on the ERK1/2 MAPK pathway to alleviate the NPP.","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569296","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

Role of adenosine in the pathophysiology and treatment of attention deficit hyperactivity disorder. 腺苷在注意缺陷多动障碍的病理生理学和治疗中的作用。

IF 3 4区医学

Purinergic Signalling Pub Date : 2024-10-31 DOI: 10.1007/s11302-024-10059-2

Qingxia Jia, Hongwan Tan, Tingsong Li, Xiaoling Duan

引用次数: 0

P2Y12 receptor-mediated cyclooxygenase 2 (COX-2) expression enhances tumor cell progression in a mouse model of lymphoma. 在小鼠淋巴瘤模型中，P2Y12 受体介导的环氧化酶 2 (COX-2) 表达可促进肿瘤细胞的发展。

IF 3 4区医学

Purinergic Signalling Pub Date : 2024-10-29 DOI: 10.1007/s11302-024-10057-4

Shilpa Sharma, Khagendra Ghimeray, Md Mostafizur Rahman, Aparna Upadrasta, Ravi Shankar Akundi

{"title":"P2Y12 receptor-mediated cyclooxygenase 2 (COX-2) expression enhances tumor cell progression in a mouse model of lymphoma.","authors":"Shilpa Sharma, Khagendra Ghimeray, Md Mostafizur Rahman, Aparna Upadrasta, Ravi Shankar Akundi","doi":"10.1007/s11302-024-10057-4","DOIUrl":"https://doi.org/10.1007/s11302-024-10057-4","url":null,"abstract":"The pro-inflammatory enzyme cyclooxygenase 2 (COX-2) has been known to impart metastatic property to cancer cells. However, blocking of COX-2 with nonsteroidal anti-inflammatory drugs or COX-2-specific inhibitors has failed in clinical trials due to adverse effects associated with their prolonged use. We have previously shown that extracellular ATP (eATP), a major component of the tumor microenvironment, enhances COX-2 expression several-fold, both in macrophages and in various cancer cells, by acting on purinergic (P2) receptors. In this study, we show that blocking of P2 receptors significantly reduced tumor growth in a mouse model of lymphoma. Tumors were induced in mice through subcutaneous injection of syngeneic EL4 lymphoma cells. Various P2 receptor antagonists were injected within the tumors after they were palpable. The broad-spectrum P2 receptor antagonist, suramin, P2X7 receptor-specific antagonist, oATP, P2Y6 receptor-specific antagonist, MRS 2578, and P2Y12 receptor-specific antagonist, AR-C 69931, all showed significant arrest in tumor growth. Both suramin and AR-C 69931-treated tumors showed strong reduction in COX-2 expression and modulation of various metastatic markers. Disaggregated cells from AR-C 69931-treated tumors, when injected intravenously in naïve mice, did not exhibit metastasis in various tissues which was observed in mice injected with cells from saline-treated tumors. Our results show that blocking of P2 receptors is a therapeutic alternative to inhibit COX-2 expression, and thereby, arrest tumor progression and metastasis.","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522816","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

Screening herbal and natural product libraries to aid discovery of novel allosteric modulators of human P2X7. 筛选草药和天然产品库，帮助发现新型人类 P2X7 异构调节剂。

IF 3 4区医学

Purinergic Signalling Pub Date : 2024-10-22 DOI: 10.1007/s11302-024-10055-6

Stefan Bidula, Waraporn Piyasirananda, Hanna Bielecka, Lučka Bibič, Andrew Beekman, Leanne Stokes

{"title":"Screening herbal and natural product libraries to aid discovery of novel allosteric modulators of human P2X7.","authors":"Stefan Bidula, Waraporn Piyasirananda, Hanna Bielecka, Lučka Bibič, Andrew Beekman, Leanne Stokes","doi":"10.1007/s11302-024-10055-6","DOIUrl":"https://doi.org/10.1007/s11302-024-10055-6","url":null,"abstract":" P2X7 is an emerging therapeutic target for several disorders and diseases due to its role in inflammatory signalling. This study aimed to exploit the unique chemical libraries of plants used in traditional medicinal practices to discover novel allosteric modulators from natural sources. We identified several compounds from the NCI Natural Product library as P2X7 antagonists including confertifolin and digallic acid (IC50 values 3.86 µM and 4.05 µM). We also identified scopafungin as a novel positive allosteric modulator of hP2X7. Screening a traditional medicinal plant extract library revealed 39 plant species with inhibitory action at hP2X7 and 17 plant species with positive allosteric modulator activity. Using computational docking to filter identified components from these plant species and determine potential antagonists, we investigated nine purified chemicals including flavonoids quercetin, kaempferol, ECG, and EGCG. These were shown to inhibit ATP-induced YO-PRO-1 uptake into HEK-hP2X7 cells; however, we also showed that all four flavonoids demonstrated significant assay interference using a cell-free DNA YO-PRO-1 fluorescence test. One plant extract, Dioscorea nipponica, demonstrating positive modulator activity was investigated, and dioscin was identified as a glycoside with PAM activity in ATP-induced YO-PRO-1 uptake assay and whole-cell patch-clamp recordings. However, membrane permeabilisation was observed following application > 10 min limiting the use of dioscin as a pharmacological tool. This work describes a useful workflow with multiple assays for the identification of novel allosteric modulators for human P2X7.","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142473429","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

P2X7 receptor in macrophage polarization and its implications in neuroblastoma tumor behavior. 巨噬细胞极化中的 P2X7 受体及其对神经母细胞瘤肿瘤行为的影响

IF 3 4区医学

Purinergic Signalling Pub Date : 2024-10-19 DOI: 10.1007/s11302-024-10051-w

Carolina Adriane Bento, Vanessa Fernandes Arnaud-Sampaio, Talita Glaser, Elena Adinolfi, Robson Coutinho-Silva, Henning Ulrich, Claudiana Lameu

{"title":"P2X7 receptor in macrophage polarization and its implications in neuroblastoma tumor behavior.","authors":"Carolina Adriane Bento, Vanessa Fernandes Arnaud-Sampaio, Talita Glaser, Elena Adinolfi, Robson Coutinho-Silva, Henning Ulrich, Claudiana Lameu","doi":"10.1007/s11302-024-10051-w","DOIUrl":"https://doi.org/10.1007/s11302-024-10051-w","url":null,"abstract":"Tumor-associated macrophages (TAMs) exhibit antitumor or protumor responses related to inflammatory (or M1) and alternative (or M2) phenotypes, respectively. The P2X7 receptor plays a key role in macrophage polarization, influencing inflammation and immunosuppression. In this study, we investigated the role of the P2X7 receptor in TAMs. Using P2X7 receptor-deficient macrophages, we analyzed gene expression profiles and their implications for neuroblastoma invasion and chemoresistance. Our results showed that P2X7 receptor deficiency altered the expression of classical polarization markers, such as nitric oxide synthase 2 (Nos2) and tumor necrosis factor-α (Tnf), as well as alternative phenotype markers, including mannose receptor C-type 1 (Mrc1) and arginase 1 (Arg1). P2X7 deficiency also influenced the expression of the ectonucleotidases Entpd1 and Nt5e and other purinergic receptors, especially P2ry2, suggesting compensatory mechanisms involved in macrophage polarization. In particular, TAMs deficient in P2X7 showed a phenotype with characteristics intermideiate between resting macrophages (M0) and M1 polarization rather than the M2-type phenotype like and wild-type TAM macrophages. In addition, P2rx7-/- TAMs regulated the expression of P2X7 receptor isoforms in neuroblastoma cells, with downregulation of the P2X7 A and B isoforms leading to a decrease in chemotherapy-induced cell death. However, TAMs expressing P2X7 downregulated only the B isoform, suggesting that TAMs play a role in modulating tumor behavior through P2X7 receptor isoform regulation. Taken together, our data underscore the regulatory function of the P2X7 receptor in orchestrating alternative macrophage polarization and in the interplay between tumor cells and TAMs. These findings help to clarify the complex interplay of purinergic signaling in cancer progression and open up avenues for future research and therapeutic interventions.","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142473428","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