Purinergic Signalling最新文献_第5页

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 2.4 4区医学

Purinergic Signalling Pub Date : 2025-08-01 Epub Date: 2024-10-31 DOI: 10.1007/s11302-024-10059-2

Qingxia Jia, Hongwan Tan, Tingsong Li, Xiaoling Duan

引用次数: 0

Regulation of transcription factor function by purinergic signalling in cardiovascular diseases. 心血管疾病中嘌呤能信号对转录因子功能的调控。

IF 2.4 4区医学

Purinergic Signalling Pub Date : 2025-08-01 Epub Date: 2024-08-31 DOI: 10.1007/s11302-024-10045-8

Hao Tang, Qihang Kong, Zhewei Zhang, Wenchao Wu, Lixing Yuan, Xiaojing Liu

引用次数: 0

A_2A receptors: a new target for immunotherapy resistance in prostate cancer. A2A受体：前列腺癌免疫治疗耐药的新靶点

IF 2.4 4区医学

Purinergic Signalling Pub Date : 2025-08-01 Epub Date: 2025-05-07 DOI: 10.1007/s11302-025-10092-9

He-Xia Peng, Yong Tang

引用次数: 0

P2X3 receptors in the paraventricular hypothalamus: a specific target for visceral pain. 室旁下丘脑中的P2X3受体：内脏疼痛的特定靶点。

IF 2.4 4区医学

Purinergic Signalling Pub Date : 2025-08-01 Epub Date: 2025-06-20 DOI: 10.1007/s11302-025-10099-2

Xiu-Min Hu, Yong Tang, Peter Illes

{"title":"P2X3 receptors in the paraventricular hypothalamus: a specific target for visceral pain.","authors":"Xiu-Min Hu, Yong Tang, Peter Illes","doi":"10.1007/s11302-025-10099-2","DOIUrl":"10.1007/s11302-025-10099-2","url":null,"abstract":"In a recent article published in Neuron, Li et al. (Neuron 112(22):3734-3749.e5, 2024) accomplished a major scientific advance by reporting that ATP-sensitive P2X3 receptor-channels (P2X3Rs) in the paraventricular hypothalamus (PVH) specifically regulate visceral pain without affecting somatic pain. On the other hand, vasoactive intestinal polypeptide-sensing receptors (VIPR2) selectively process somatic pain without altering visceral pain. Function-dependent laser capture microdissection sequencing (fLCM-Seq) and immunohistochemistry demonstrated that P2X3Rs and VIPR2 have different transcriptional profiles and belong to the colorectal distension (CRD) and von Frey filament (VFF)-stimulated subgroups of PVH neurons, respectively. An anterograde tracing strategy, in which green fluorescent protein (GFP) was selectively expressed in CRD-labeled or VFF-labeled PVH neurons, showed that PVHP2X3R+ neuronal projections terminated exclusively at the ventral part of the lateral septal nucleus (LSV) while the PVHVIPR2+ neuronal projections terminated at the caudal part of the zona incerta (ZIC). The PVHP2X3R+ circuit selectively responded to visceral pain while remaining unresponsive to somatic pain. By contrast, the PVHVIPR2+ circuit selectively responded to somatic pain, while it did not react to visceral pain. Knockdown of P2X3R expression in PVH neurons enhanced the visceral pain threshold without affecting somatic nociception, and the reverse findings were true for the knockdown of the VIPR2 expressing PVH neurons. All these results provide possible new strategies based on central-targeted therapies for the future treatment of visceral and somatic pain, respectively.","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":"987-989"},"PeriodicalIF":2.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12454728/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333818","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

Correction to: The role of purinergic P2X3 receptors and endometriosis-associated hyperalgesia. 更正：嘌呤能P2X3受体与子宫内膜异位症相关痛觉过敏的作用。

IF 2.4 4区医学

Purinergic Signalling Pub Date : 2025-07-30 DOI: 10.1007/s11302-025-10106-6

Kailane Paula Pretto, Letícia de Souza Matias, Bruna Dias de Oliveira, Adinei Abadio Soares, Camila Ferreira Puntel, Yghor Augusto da Rocha Ricardo, Yenidis Teilor Scheibel, Débora Tavares de Resende E Silva

引用次数: 0

The role of purinergic P2X3 receptors and endometriosis-associated hyperalgesia. 嘌呤能P2X3受体在子宫内膜异位症相关痛觉过敏中的作用。

IF 2.4 4区医学

Purinergic Signalling Pub Date : 2025-07-04 DOI: 10.1007/s11302-025-10101-x

Kailane Paula Pretto, Letícia de Souza Matias, Bruna Dias de Oliveira, Adinei Abadio Soares, Camila Ferreira Puntel, Yghor Augusto da Rocha Ricardo, Yenidis Teilor Scheibel, Débora Tavares de Resende E Silva

{"title":"The role of purinergic P2X3 receptors and endometriosis-associated hyperalgesia.","authors":"Kailane Paula Pretto, Letícia de Souza Matias, Bruna Dias de Oliveira, Adinei Abadio Soares, Camila Ferreira Puntel, Yghor Augusto da Rocha Ricardo, Yenidis Teilor Scheibel, Débora Tavares de Resende E Silva","doi":"10.1007/s11302-025-10101-x","DOIUrl":"10.1007/s11302-025-10101-x","url":null,"abstract":"Endometriosis is a chronic gynecological condition characterized by endometrial tissue outside the uterine cavity. Recent research has focused on the relationship between the purinergic system and endometriosis. As a purinergic system component, extracellular adenosine triphosphate (ATP) has been involved as a crucial mediator of chronic pain associated with the disease, as well as P2X3 receptors, which play a key role in sensitization of nerve fibers and generation of nociceptive, neuropathic, and inflammatory pain. In addition, ectonucleotidases such as CD39 and CD73, which regulate ATP hydrolysis, have an altered expression in endometriotic lesions, contributing to extracellular ATP accumulation, intensifying inflammation and pain. Together, immune cells and their product are increased in endometriotic foci and promote the emergence of new lesions through their contribution to retrograde menstruation. Some studies have observed significant changes in mitochondrial respiration, notably decreased oxygen consumption in the affected endometrium. These various cellular processes that are mediated by ATP and adenosine in the uterine cavity and exert effects on immune defense will be herein reviewed in detail to investigate possible inhibitors, their activity, and potential exploration of the purinergic pathway as a therapeutic alternative.","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560967","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 CALHM1 blocker CGP37157 increases seizure severity during status epilepticus in adult mice. CALHM1阻滞剂CGP37157增加成年小鼠癫痫持续状态期间癫痫发作的严重程度。

IF 3 4区医学

Purinergic Signalling Pub Date : 2025-07-02 DOI: 10.1007/s11302-025-10103-9

Meghma Mitra, Amaya Sanz Rodriguez, Norman Delanty, Alan Beausang, Francesca M Brett, Michael A Farrell, Jane Cryan, Donncha F O'Brien, David Henshall, Maria F Cano-Abad, Tobias Engel

{"title":"The CALHM1 blocker CGP37157 increases seizure severity during status epilepticus in adult mice.","authors":"Meghma Mitra, Amaya Sanz Rodriguez, Norman Delanty, Alan Beausang, Francesca M Brett, Michael A Farrell, Jane Cryan, Donncha F O'Brien, David Henshall, Maria F Cano-Abad, Tobias Engel","doi":"10.1007/s11302-025-10103-9","DOIUrl":"https://doi.org/10.1007/s11302-025-10103-9","url":null,"abstract":"Epilepsy is one of the most common chronic brain diseases affecting up to 70 million people worldwide. Major challenges of epilepsy treatment include the high pharmacoresistance in patients and the lack of disease-modification. Extracellular adenosine 3'triphosphate (ATP), a key neurotransmitter in the activation of the purinergic signalling system, is increasingly recognized to contribute to pathological brain hyperexcitability in epilepsy. Consequently, targeting ATP-release mechanisms may constitute a new therapeutic strategy for seizure control and epilepsy. The calcium channel, Calcium Homeostasis Modulator 1 (CALHM1), a voltage-gated, non-selective ion channel that permits the passage of various cations and small molecules, is expressed in neurons and plays an essential role during neuronal excitability and neurotransmission. In addition to ions, CALHM1 also allows the passage of ATP into the extracellular space, activating thereby purinergic receptors. Here, we tested if the pharmacological blocking of CALHM1 via CGP37157 (7-chloro-5-(2-chlorophenyl)-3,5-dihydro-4,1-benzothiazepin-2-(1H)-one) alters the severity of intra-amygdala kainic acid-induced status epilepticus. Our results show that CGP37157 increased the severity of seizures during status epilepticus. In addition, CALHM1 protein levels are down-regulated in the hippocampus in epileptic mice and Temporal Lobe Epilepsy (TLE) patients. In summary, our results identify CALHM1 as a new contributor to seizures and suggest targeting of CALHM1 as new treatment strategy for epilepsy.","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144542056","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

Acute effects of guanosine or inosine in a porcine model of hemorrhagic shock. 鸟苷或肌苷在猪失血性休克模型中的急性作用。

IF 3 4区医学

Purinergic Signalling Pub Date : 2025-06-17 DOI: 10.1007/s11302-025-10097-4

André P Schmidt, Denise A Otsuki, Gisele Hansel, Jean P Oses, Carolina D Wiener, Fernanda P Moreira, Luís V Portela, Diogo O Souza, Jose O C Auler

{"title":"Acute effects of guanosine or inosine in a porcine model of hemorrhagic shock.","authors":"André P Schmidt, Denise A Otsuki, Gisele Hansel, Jean P Oses, Carolina D Wiener, Fernanda P Moreira, Luís V Portela, Diogo O Souza, Jose O C Auler","doi":"10.1007/s11302-025-10097-4","DOIUrl":"https://doi.org/10.1007/s11302-025-10097-4","url":null,"abstract":"Hemorrhagic shock (HS) leads to systemic hypoperfusion, impaired tissue oxygenation, and multi-organ dysfunction, including central nervous system (CNS) injury. Guanosine and inosine, purine nucleosides with neuroprotective and anti-inflammatory properties, have demonstrated beneficial effects in models of neurotoxicity, ischemia, and septic shock. This study evaluated the acute effects of guanosine and inosine in fluid resuscitation, focusing on brain energy metabolism, neuroinflammatory mechanisms, and hemodynamic responses in a porcine model of HS. Thirty pigs (25-30 kg) underwent controlled hemorrhage to achieve a target mean arterial pressure (MAP) of 40 - 45 mmHg, maintained for 60 min. Animals were randomized into three resuscitation groups: Lactated Ringer's solution (LR), LR + guanosine (1 mmol/L), and LR + inosine (1 mmol/L), administered over 15 - 20 min. Hemodynamic, metabolic, and neuronal parameters were monitored for 440 min post-HS, with serial blood and cerebrospinal fluid (CSF) sampling to assess glutamate, lactate, glucose, neuron-specific enolase (NSE), and inflammatory cytokines. HS induced metabolic acidosis, increased CSF glutamate levels, and elevated proinflammatory cytokines (IL-1β, TNF-α, IFN-γ, IL-8). Guanosine and inosine reduced glutamate levels more rapidly than LR alone and attenuated IL-1β and TNF-α elevations. Inosine resuscitation improved MAP, systemic vascular resistance index (SVRI), and end-diastolic volume index (EDVI), suggesting enhanced hemodynamic stabilization. Guanosine and inosine modulated neuroinflammatory and metabolic responses in HS, reducing excitotoxicity and inflammatory cytokine release. Inosine also demonstrated hemodynamic benefits. These findings support further investigation into their therapeutic potential in shock resuscitation.","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317806","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

Depletion of P2X4 receptor alleviates prostate cancer bone metastasis through reduced cancer cell invasiveness and enhanced cell adhesion activities. P2X4受体的缺失通过降低癌细胞侵袭性和增强细胞粘附活性来缓解前列腺癌骨转移。

IF 3 4区医学

Purinergic Signalling Pub Date : 2025-06-14 DOI: 10.1007/s11302-025-10096-5

Jiepei He, Yuhan Zhou, Hector M Arredondo Carrera, Nan Li, Alison Gartland, Ning Wang

{"title":"Depletion of P2X4 receptor alleviates prostate cancer bone metastasis through reduced cancer cell invasiveness and enhanced cell adhesion activities.","authors":"Jiepei He, Yuhan Zhou, Hector M Arredondo Carrera, Nan Li, Alison Gartland, Ning Wang","doi":"10.1007/s11302-025-10096-5","DOIUrl":"https://doi.org/10.1007/s11302-025-10096-5","url":null,"abstract":"Prostate cancer (PCa) preferentially metastasizes to bone, which remains incurable and contributes significantly to mortality and morbidity. The P2X4 receptor (P2X4R) is a receptor for ATP that is highly expressed in many cancer types including PCa and is positively associated with tumorigenesis. To understand the role of P2X4R in PCa biology, particularly in PCa bone metastasis, P2X4R (P2RX4) was knocked out in human PCa cell line PC3 cells using the CRISPR/Cas9 system. Cell proliferation, apoptosis, migration, and invasion were examined using CyQUANT, Cell Meter Caspase 3/7, scratch and transwell assays. Results showed that depleting P2X4R significantly reduced cell proliferation and invasion and increased apoptosis compared to PC3 wildtype (WT) controls in vitro. To test their metastatic potential in vivo, PC3 WT and knock-out (KO) cells were intracardiacally injected into male BALB/c immunocompromised mice. Twenty-five days post-injection, there were no detectable tumours and associated bone destruction in the tibias of mice injected with KO cells, whereas tibias of over 50% mice injected with WT cells were occupied by tumour cells, with significant bone destruction observed ex vivo using micro-CT. Furthermore, RNA-seq and bioinformatic analysis of P2X4R KO cells demonstrated links between P2X4R and PCa cell adhesion, and other key signalling such as Wnt signalling. These findings suggest that P2X4R is a potential therapeutic target for PCa metastasis, particularly bone metastasis.","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144294846","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

ATP who you are. ATP你是谁。

IF 3 4区医学

Purinergic Signalling Pub Date : 2025-06-12 DOI: 10.1007/s11302-025-10098-3

Yong Tang, Peter Illes

引用次数: 0