Purinergic Signalling最新文献_第9页

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

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

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

Heterologous expression and biochemical characterization of the recombinant nucleoside triphosphate diphosphohydrolase 2 (LbNTPDase2) from Leishmania (Viannia) braziliensis. 巴西利什曼原虫重组核苷三磷酸二磷酸水解酶2 (LbNTPDase2)的异源表达及生化特性研究。

IF 3 4区医学

Purinergic Signalling Pub Date : 2024-10-01 Epub Date: 2023-11-24 DOI: 10.1007/s11302-023-09980-9

Nancy da Rocha Torres Pavione, João Victor Badaró de Moraes, Isadora Cunha Ribeiro, Raissa Barbosa de Castro, Walmir da Silva, Anna Cláudia Alves de Souza, Victor Hugo Ferraz da Silva, Raphael de Souza Vasconcellos, Gustavo da Costa Bressan, Juliana Lopes Rangel Fietto

{"title":"Heterologous expression and biochemical characterization of the recombinant nucleoside triphosphate diphosphohydrolase 2 (LbNTPDase2) from Leishmania (Viannia) braziliensis.","authors":"Nancy da Rocha Torres Pavione, João Victor Badaró de Moraes, Isadora Cunha Ribeiro, Raissa Barbosa de Castro, Walmir da Silva, Anna Cláudia Alves de Souza, Victor Hugo Ferraz da Silva, Raphael de Souza Vasconcellos, Gustavo da Costa Bressan, Juliana Lopes Rangel Fietto","doi":"10.1007/s11302-023-09980-9","DOIUrl":"10.1007/s11302-023-09980-9","url":null,"abstract":"Leishmania braziliensis is a pathogenic protozoan parasite that causes American Tegumentary Leishmaniasis (ATL), an important tropical neglected disease. ENTPDases are nucleotidases that hydrolyze intracellular and/or extracellular nucleotides. ENTPDases are known as regulators of purinergic signalling induced by extracellular nucleotides. Leishmania species have two isoforms of ENTPDase, and, particularly, ENTPDase2 seems to be involved in infectivity and virulence. In this study, we conducted the heterologous expression and biochemical characterization of the recombinant ENTPDase2 of L. braziliensis (rLbNTPDase2). Our results show that this enzyme is a canonical ENTPDase with apyrase activity, capable of hydrolysing triphosphate and diphosphate nucleotides, and it is dependent on divalent cations (calcium or magnesium). Substrate specificity was characterized as UDP>GDP>ADP>GTP>ATP=UTP. The enzyme showed optimal activity at a neutral to basic pH and was partially inhibited by suramin and DIDS. Furthermore, the low apparent Km for ADP suggests that the enzyme may play a role in adenosine-mediated signalling. The biochemical characterization of this enzyme can open new avenues for using LbNTPDase2 as a drug target.","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":"509-520"},"PeriodicalIF":3.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377403/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138299840","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

Role of CD73 and the purinergic signaling pathway in the pathogenesis of fusion-negative rhabdomyosarcoma. CD73和嘌呤能信号通路在融合阴性横纹肌肉瘤发病机制中的作用

IF 3 4区医学

Purinergic Signalling Pub Date : 2024-10-01 Epub Date: 2024-05-03 DOI: 10.1007/s11302-024-10013-2

Amelia Fascì, Silvia Deaglio

引用次数: 0

Preclinical and clinical aspects of P2X receptors as a common route in different diseases: A meeting report. P2X 受体作为不同疾病共同途径的临床前和临床方面：会议报告。

IF 3 4区医学

Purinergic Signalling Pub Date : 2024-10-01 Epub Date: 2024-02-20 DOI: 10.1007/s11302-024-09994-x

Luke Tattersall, Elena Adinolfi, Luca Antonioli, Ankita Agrawal

引用次数: 0

Regulation of nerve-evoked contractions of the murine vas deferens. 神经诱发小鼠输精管收缩的调节。

IF 3 4区医学

Purinergic Signalling Pub Date : 2024-10-01 Epub Date: 2024-02-20 DOI: 10.1007/s11302-024-09993-y

Pei Yee Wong, Zhihui Fong, Mark A Hollywood, Keith D Thornbury, Gerard P Sergeant

{"title":"Regulation of nerve-evoked contractions of the murine vas deferens.","authors":"Pei Yee Wong, Zhihui Fong, Mark A Hollywood, Keith D Thornbury, Gerard P Sergeant","doi":"10.1007/s11302-024-09993-y","DOIUrl":"10.1007/s11302-024-09993-y","url":null,"abstract":"Stimulation of sympathetic nerves in the vas deferens yields biphasic contractions consisting of a rapid transient component resulting from activation of P2X1 receptors by ATP and a secondary sustained component mediated by activation of α1-adrenoceptors by noradrenaline. Noradrenaline can also potentiate the ATP-dependent contractions of the vas deferens, but the mechanisms underlying this effect are unclear. The purpose of the present study was to investigate the mechanisms underlying potentiation of transient contractions of the vas deferens induced by activation of α1-adrenoceptors. Contractions of the mouse vas deferens were induced by electric field stimulation (EFS). Delivery of brief (1s duration) pulses (4 Hz) yielded transient contractions that were inhibited tetrodotoxin (100 nM) and guanethidine (10 µM). α,β-meATP (10 µM), a P2X1R desensitising agent, reduced the amplitude of these responses by 65% and prazosin (100 nM), an α1-adrenoceptor antagonist, decreased mean contraction amplitude by 69%. Stimulation of α1-adrenoceptors with phenylephrine (3 µM) enhanced EFS and ATP-induced contractions and these effects were mimicked by the phorbol ester PDBu (1 µM), which activates PKC. The PKC inhibitor GF109203X (1 µM) prevented the stimulatory effects of PDBu on ATP-induced contractions of the vas deferens but only reduced the stimulatory effects of phenylephrine by 40%. PDBu increased the amplitude of ATP-induced currents recorded from freshly isolated vas deferens myocytes and HEK-293 cells expressing human P2X1Rs by 93%. This study indicates that: (1) potentiation of ATP-evoked contractions of the mouse vas deferens by α1-adrenoceptor activation were not fully blocked by the PKC inhibitor GF109203X and (2) that the stimulatory effect of PKC on ATP-induced contractions of the vas deferens is associated with enhanced P2X1R currents in vas deferens myocytes.","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":"547-557"},"PeriodicalIF":3.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377391/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139906394","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

Genetic and functional modulation by agonist MRS5698 and allosteric enhancer LUF6000 at the native A₃ adenosine receptor in HL-60 cells. 激动剂 MRS5698 和异位增强剂 LUF6000 对 HL-60 细胞中原生 A3 腺苷受体的遗传和功能调节。

IF 3 4区医学

Purinergic Signalling Pub Date : 2024-10-01 Epub Date: 2024-02-28 DOI: 10.1007/s11302-024-09992-z

Zhan-Guo Gao, Weiping Chen, Ray R Gao, Jonathan Li, Dilip K Tosh, John A Hanover, Kenneth A Jacobson

{"title":"Genetic and functional modulation by agonist MRS5698 and allosteric enhancer LUF6000 at the native A3 adenosine receptor in HL-60 cells.","authors":"Zhan-Guo Gao, Weiping Chen, Ray R Gao, Jonathan Li, Dilip K Tosh, John A Hanover, Kenneth A Jacobson","doi":"10.1007/s11302-024-09992-z","DOIUrl":"10.1007/s11302-024-09992-z","url":null,"abstract":"The A3 adenosine receptor (AR) is an important inflammatory and immunological target. However, the underlying mechanisms are not fully understood. Here, we report the gene regulation in HL-60 cells treated acutely with highly selective A3AR agonist MRS5698, positive allosteric modulator (PAM) LUF6000, or both. Both pro- and anti-inflammatory genes, such as IL-1a, IL-1β, and NFκBIZ, are significantly upregulated. During our observations, LUF6000 alone produced a lesser effect, while the MRS5698 + LUF6000 group demonstrated generally greater effects than MRS5698 alone, consistent with allosteric enhancement. The number of genes up- and down-regulated are similar. Pathway analysis highlighted the critical involvement of signaling molecules, including IL-6 and IL-17. Important upstream regulators include IL-1a, IL-1β, TNF-α, NF-κB, etc. PPAR, which modulates eicosanoid metabolism, was highly downregulated by the A3AR agonist. Considering previous pharmacological results and mathematical modeling, LUF6000's small enhancement of genetic upregulation suggested that MRS5698 is a nearly full agonist, which we demonstrated in both cAMP and calcium assays. The smaller effect of LUF6000 on MRS5698 in comparison to its effect on Cl-IB-MECA was shown in both HL-60 cells endogenously expressing the human (h) A3AR and in recombinant hA3AR-expressing CHO cells, consistent with its HL-60 cell genetic regulation patterns. In summary, by using both selective agonists and PAM, we identified genes that are closely relevant to immunity and inflammation to be regulated by A3AR in differentiated HL-60 cells, a cell model of neutrophil function. In addition, we demonstrated the previously uncharacterized allosteric signaling-enhancing effect of LUF6000 in cells endogenously expressing the hA3AR.","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":"559-570"},"PeriodicalIF":3.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377395/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139983636","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

Novel synthesized ionizable lipid for LNP-mediated P2X7siRNA to inhibit migration and induce apoptosis of breast cancer cells. 用于 LNP 介导的 P2X7siRNA 抑制乳腺癌细胞迁移并诱导其凋亡的新型可离子化脂质合成物。

IF 3 4区医学

Purinergic Signalling Pub Date : 2024-10-01 Epub Date: 2024-03-04 DOI: 10.1007/s11302-024-09989-8

Seyed Hossein Kiaie, Ali Rajabi Zangi, Mohammad Sheibani, Salar Hemmati, Behzad Baradaran, Hadi Valizadeh

{"title":"Novel synthesized ionizable lipid for LNP-mediated P2X7siRNA to inhibit migration and induce apoptosis of breast cancer cells.","authors":"Seyed Hossein Kiaie, Ali Rajabi Zangi, Mohammad Sheibani, Salar Hemmati, Behzad Baradaran, Hadi Valizadeh","doi":"10.1007/s11302-024-09989-8","DOIUrl":"10.1007/s11302-024-09989-8","url":null,"abstract":"The development of ionizable lipid (IL) was necessary to enable the effective formulation of small interfering RNA (siRNA) to inhibit P2X7 receptors (P2X7R), a key player in tumor proliferation, apoptosis, and metastasis. In this way, the synthesis and utility of IL for enhancing cellular uptake of lipid nanoparticles (LNP) improve the proper delivery of siRNA-LNPs for knockdown overexpression of P2X7R. Therefore, to evaluate the impact of P2X7 knockdown on breast cancer (BC) migration and apoptosis, a branched and synthesized ionizable lipid (SIL) was performed for efficient transfection of LNP with siRNA for targeting P2X7 receptors (siP2X7) in mouse 4T-1 cells. Following synthesis and structural analysis of SIL, excellent characterization of the LNP was achieved (Z-average 126.8 nm, zeta-potential - 12.33, PDI 0.16, and encapsulation efficiency 85.35%). Afterward, the stability of the LNP was evaluated through an analysis of the leftover composition, and toxic concentration values for SIL and siP2X7 were determined. Furthermore, siP2X7-LNP cellular uptake in the formulation was assessed via confocal microscopy. Following determining the optimal dose (45 pmol), wound healing analysis was assessed using scratch assay microscopy, and apoptosis was evaluated using flow cytometry. The use of the innovative branched SIL in the formulation of siP2X7-LNP resulted in significant inhibition of migration and induction of apoptosis in 4T-1 cells due to improved cellular uptake. Subsequently, the innovative SIL represents a critical role in efficiently delivering siRNA against murine triple-negative breast cancer cells (TNBC) using LNP formulation, resulting in significant efficacy.","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":"533-546"},"PeriodicalIF":3.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377399/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140022519","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