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Pharmacology of pannexin channels 血管紧张素通道的药理学
IF 4 3区 医学
Current Opinion in Pharmacology Pub Date : 2023-04-01 DOI: 10.1016/j.coph.2023.102359
Michael Koval , Wyatt J. Schug , Brant E. Isakson
{"title":"Pharmacology of pannexin channels","authors":"Michael Koval ,&nbsp;Wyatt J. Schug ,&nbsp;Brant E. Isakson","doi":"10.1016/j.coph.2023.102359","DOIUrl":"10.1016/j.coph.2023.102359","url":null,"abstract":"<div><p>Pannexin channels play fundamental roles in regulating inflammation and have been implicated in many diseases including hypertension, stroke, and neuropathic pain. Thus, the ability to pharmacologically block these channels is a vital component of several therapeutic approaches. Pharmacologic interrogation of model systems also provides a means to discover new roles for pannexins in cell physiology. Here, we review the state of the art for agents that can be used to block pannexin channels, with a focus on chemical pharmaceuticals and peptide mimetics that act on pannexin 1. Guidance on interpreting results obtained with pannexin pharmacologics in experimental systems is discussed, as well as strengths and caveats of different agents, including specificity and feasibility of clinical application.</p></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":"69 ","pages":"Article 102359"},"PeriodicalIF":4.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10023479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9512943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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: 10
The role of extracellular ATP and P2X receptors in the pathogenesis of HIV-1 细胞外ATP和P2X受体在HIV-1发病机制中的作用
IF 4 3区 医学
Current Opinion in Pharmacology Pub Date : 2023-04-01 DOI: 10.1016/j.coph.2023.102358
Natalia R. Rodriguez, Trinisia Fortune, Thien Vuong, Talia H. Swartz
{"title":"The role of extracellular ATP and P2X receptors in the pathogenesis of HIV-1","authors":"Natalia R. Rodriguez,&nbsp;Trinisia Fortune,&nbsp;Thien Vuong,&nbsp;Talia H. Swartz","doi":"10.1016/j.coph.2023.102358","DOIUrl":"10.1016/j.coph.2023.102358","url":null,"abstract":"<div><p><span><span>Human Immunodeficiency Virus Type 1 (HIV-1) causes a chronic, incurable infection associated with </span>chronic inflammation<span> despite virologic suppression on antiretroviral therapy (ART). This chronic inflammation underlies significant comorbidities, including cardiovascular disease, neurocognition decline, and malignancies. The mechanisms of chronic inflammation have been attributed, in part, to the role of extracellular ATP and P2X-type purinergic receptors<span><span> that sense damaged or dying cells and undergo signaling responses to activate inflammation and immunomodulation. This review describes the current literature on the role of extracellular ATP and </span>P2X receptors in HIV-1 pathogenesis, describing the known intersection with the HIV-1 life cycle in mediating </span></span></span>immunopathogenesis<span> and neuronal disease. The literature supports key roles for this signaling mechanism in cell-to-cell communication and in activating transcriptional changes that impact the inflammatory state leading to disease progression. Future studies must characterize the numerous functions of ATP and P2X receptors in HIV-1 pathogenesis to inform future therapeutic targeting.</span></p></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":"69 ","pages":"Article 102358"},"PeriodicalIF":4.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10023410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9142018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
The blood pressure lowering effects of glucagon-like peptide-1 receptor agonists: A mini-review of the potential mechanisms 胰高血糖素样肽-1受体激动剂的降压作用：潜在机制的初步综述
IF 4 3区 医学
Current Opinion in Pharmacology Pub Date : 2023-04-01 DOI: 10.1016/j.coph.2023.102355
Joao Carlos Ribeiro-Silva , Caio A.M. Tavares , Adriana C.C. Girardi
{"title":"The blood pressure lowering effects of glucagon-like peptide-1 receptor agonists: A mini-review of the potential mechanisms","authors":"Joao Carlos Ribeiro-Silva ,&nbsp;Caio A.M. Tavares ,&nbsp;Adriana C.C. Girardi","doi":"10.1016/j.coph.2023.102355","DOIUrl":"10.1016/j.coph.2023.102355","url":null,"abstract":"<div><p>The incretin hormone<span><span> glucagon-like peptide 1 (GLP-1) is a key component of the signaling mechanisms promoting glucose homeostasis. Clinical and experimental studies demonstrated that GLP-1 receptor agonists, including GLP-1 itself, have favorable effects on blood pressure and reduce the risk of major cardiovascular events, independently of their effect on glycemic control. GLP-1 receptors are present in the hypothalamus and brainstem, the </span>carotid body, the vasculature, and the kidneys. These organs are involved in blood pressure regulation, have their function altered in hypertension, and are positively benefited by the treatment with GLP-1 receptor agonists. Here, we discuss the potential mechanisms whereby activation of GLP-1R signaling exerts blood pressure-lowering effects beyond glycemic control.</span></p></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":"69 ","pages":"Article 102355"},"PeriodicalIF":4.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9143693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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: 1
Editorial overview: Immune regulation and cancers 编辑综述：免疫调节与癌症
IF 4 3区 医学
Current Opinion in Pharmacology Pub Date : 2023-04-01 DOI: 10.1016/j.coph.2023.102360
Carlotta Giorgi, Shafi Kuchay
{"title":"Editorial overview: Immune regulation and cancers","authors":"Carlotta Giorgi,&nbsp;Shafi Kuchay","doi":"10.1016/j.coph.2023.102360","DOIUrl":"10.1016/j.coph.2023.102360","url":null,"abstract":"","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":"69 ","pages":"Article 102360"},"PeriodicalIF":4.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10002678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
How organoids can improve personalized treatment in patients with gastro-esophageal tumors 类器官如何改善胃食管肿瘤患者的个性化治疗
IF 4 3区 医学
Current Opinion in Pharmacology Pub Date : 2023-04-01 DOI: 10.1016/j.coph.2023.102348
Manuel Cabeza-Segura , Blanca Garcia-Micò , Marcella La Noce , Giovanni Francesco Nicoletti , Valeria Conti , Amelia Filippelli , Tania Fleitas , Andrés Cervantes , Josefa Castillo , Federica Papaccio
{"title":"How organoids can improve personalized treatment in patients with gastro-esophageal tumors","authors":"Manuel Cabeza-Segura ,&nbsp;Blanca Garcia-Micò ,&nbsp;Marcella La Noce ,&nbsp;Giovanni Francesco Nicoletti ,&nbsp;Valeria Conti ,&nbsp;Amelia Filippelli ,&nbsp;Tania Fleitas ,&nbsp;Andrés Cervantes ,&nbsp;Josefa Castillo ,&nbsp;Federica Papaccio","doi":"10.1016/j.coph.2023.102348","DOIUrl":"10.1016/j.coph.2023.102348","url":null,"abstract":"<div><p>Gastro-esophageal tumors constitute a big health problem. Treatment options still mainly rely on chemotherapy, and apart from human epidermal growth factor receptor 2<span> positive and microsatellite<span> instable/Epstein–Barr Virus disease, there are no molecularly guided options. Therefore, despite the large number of identified molecular alterations, precision medicine is still far from the clinic. In this context, the recently developed technology of patient-derived organoids (PDOs) could offer the chance to accelerate drug development and biomarker discovery. Indeed, PDOs are 3D primary cultures that were shown to reproduce patient's tumor characteristics. Moreover, several reports indicated that PDOs can replicate patient's response to a given drug; therefore, they are one of the most promising tools for functional precision medicine.</span></span></p></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":"69 ","pages":"Article 102348"},"PeriodicalIF":4.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9497218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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: 3
The P2X7 purinoceptor in pathogenesis and treatment of dystrophino- and sarcoglycanopathies P2X7嘌呤受体在肌营养不良和肌多糖病的发病机制和治疗中的作用
IF 4 3区 医学
Current Opinion in Pharmacology Pub Date : 2023-04-01 DOI: 10.1016/j.coph.2023.102357
Dariusz C. Gόrecki, Robin M.H. Rumney
{"title":"The P2X7 purinoceptor in pathogenesis and treatment of dystrophino- and sarcoglycanopathies","authors":"Dariusz C. Gόrecki,&nbsp;Robin M.H. Rumney","doi":"10.1016/j.coph.2023.102357","DOIUrl":"10.1016/j.coph.2023.102357","url":null,"abstract":"<div><p>Dystrophinopathy and sarcoglycanopathies are incurable diseases caused by mutations in the genes encoding dystrophin or members of the dystrophin associated protein complex (DAPC). Restoration of the missing dystrophin or sarcoglycans <em>via</em> genetic approaches is complicated by the downsides of personalised medicines and immune responses against re-expressed proteins. Thus, the targeting of disease mechanisms downstream from the mutant protein has a strong translational potential. Acute muscle damage causes release of large quantities of ATP, which activates P2X7 purinoceptors, resulting in inflammation that clears dead tissues and triggers regeneration. However, in dystrophic muscles, loss of α-sarcoglycan ecto-ATPase activity further elevates extracellular ATP (eATP) levels, exacerbating the pathology. Moreover, seemingly compensatory P2X7 upregulation in dystrophic muscle cells, combined with high eATP leads to further damage. Accordingly, P2X7 blockade alleviated dystrophic damage in mouse models of both dystrophinopathy and sarcoglycanopathy. Existing P2X7 blockers could be re-purposed for the treatment of these highly debilitating diseases.</p></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":"69 ","pages":"Article 102357"},"PeriodicalIF":4.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9497220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Purinergic signalling in graft-versus-host disease 移植物抗宿主病中的嘌呤能信号传导
IF 4 3区 医学
Current Opinion in Pharmacology Pub Date : 2023-02-01 DOI: 10.1016/j.coph.2022.102346
Ronald Sluyter , Peter Cuthbertson , Amal Elhage , Chloe Sligar , Debbie Watson
{"title":"Purinergic signalling in graft-versus-host disease","authors":"Ronald Sluyter ,&nbsp;Peter Cuthbertson ,&nbsp;Amal Elhage ,&nbsp;Chloe Sligar ,&nbsp;Debbie Watson","doi":"10.1016/j.coph.2022.102346","DOIUrl":"10.1016/j.coph.2022.102346","url":null,"abstract":"<div><p><span>Allogeneic hematopoietic stem cell<span><span><span> transplantation is used to treat blood cancers, but often results in lethal graft-versus-host disease (GVHD). GVHD is an inflammatory disorder mediated by donor leukocytes that damage host tissues. Purinergic signalling plays important roles in GVHD development in mice but studies of these pathways in human GVHD remain limited. P2X7 receptor activation by ATP on host </span>antigen presenting cells contributes to the induction of GVHD, while activation of this receptor on regulatory </span>T cells, myeloid-derived suppressor cells and possibly type 3 innate lymphoid cells results in their loss to promote GVHD progression. In contrast, A</span></span><sub>2A</sub> receptor activation by adenosine on donor T cells serves to restrict GVHD development. These and other purinergic signalling molecules remain potential biomarkers and therapeutic targets in GVHD.</p></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":"68 ","pages":"Article 102346"},"PeriodicalIF":4.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10834930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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: 2
The use of hormone stimulation in male infertility 激素刺激在男性不育中的应用
IF 4 3区 医学
Current Opinion in Pharmacology Pub Date : 2023-02-01 DOI: 10.1016/j.coph.2022.102333
Daniel Foran , Runzhi Chen , Channa N. Jayasena , Suks Minhas , Tharu Tharakan
{"title":"The use of hormone stimulation in male infertility","authors":"Daniel Foran ,&nbsp;Runzhi Chen ,&nbsp;Channa N. Jayasena ,&nbsp;Suks Minhas ,&nbsp;Tharu Tharakan","doi":"10.1016/j.coph.2022.102333","DOIUrl":"10.1016/j.coph.2022.102333","url":null,"abstract":"<div><p>Infertility affects 15% of couples worldwide and in approximately 50% of cases the cause is secondary to an abnormality of the sperm. However, treatment options for male infertility are limited and empirical use of hormone stimulation has been utilised. We review the contemporary data regarding the application of hormone stimulation to treat male infertility. There is strong evidence supporting the use of hormone stimulation in hypogonadotropic hypogonadism but there is inadequate evidence for all other indications.</p></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":"68 ","pages":"Article 102333"},"PeriodicalIF":4.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9339915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 role of extracellular ATP in homeostatic immune cell migration 细胞外ATP在稳态免疫细胞迁移中的作用
IF 4 3区 医学
Current Opinion in Pharmacology Pub Date : 2023-02-01 DOI: 10.1016/j.coph.2022.102331
Daichi Kobayashi , Eiji Umemoto , Masayuki Miyasaka
{"title":"The role of extracellular ATP in homeostatic immune cell migration","authors":"Daichi Kobayashi ,&nbsp;Eiji Umemoto ,&nbsp;Masayuki Miyasaka","doi":"10.1016/j.coph.2022.102331","DOIUrl":"10.1016/j.coph.2022.102331","url":null,"abstract":"<div><p>Antigen stimulation induces adenosine triphosphate (ATP) release from naïve lymphocytes in lymphoid tissues. However, previous studies indicated that the non-lytic release of ATP also occurs in most tissues and cell types under physiological conditions. Here, we show that extracellular ATP (eATP) is indeed constitutively produced by naïve T cells in response to lymphoid chemokines in uninflamed lymph nodes and is involved in the regulation of immune cell migration. In this review, we briefly summarize the homeostatic role of extracellular ATP in immune cell migration <em>in vivo</em>.</p></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":"68 ","pages":"Article 102331"},"PeriodicalIF":4.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10834389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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: 1
Non-hereditary early onset gastric cancer: An unmet medical need 非遗传性早发癌症：未满足的医疗需求
IF 4 3区 医学
Current Opinion in Pharmacology Pub Date : 2023-02-01 DOI: 10.1016/j.coph.2022.102344
Angelica Petrillo , Piera Federico , Gianpaolo Marte , Carlo Liguori , Andreas Seeber , Margaret Ottaviano , Andrea Tufo , Bruno Daniele
{"title":"Non-hereditary early onset gastric cancer: An unmet medical need","authors":"Angelica Petrillo ,&nbsp;Piera Federico ,&nbsp;Gianpaolo Marte ,&nbsp;Carlo Liguori ,&nbsp;Andreas Seeber ,&nbsp;Margaret Ottaviano ,&nbsp;Andrea Tufo ,&nbsp;Bruno Daniele","doi":"10.1016/j.coph.2022.102344","DOIUrl":"10.1016/j.coph.2022.102344","url":null,"abstract":"<div><p>Gastric cancer (GC) is a lethal disease and the diagnosis in the young population is a major challenge from both individual and social point of views. Early-onset GC accounts for ∼5% of GC; among them, 3% are part of a hereditary syndrome and the majority are sporadic. However, even if the early-onset forms were less frequent in the past, the increasing number in the last decades has improved the interest and awareness of them in the society and in the scientific community. In particular, the different behaviour and characteristics of early-onset GC suggest that it is a completely different entity, which requires a tailored and personalized management. Here we provide an updated overview about non-hereditary early-onset GC, which is an unmet clinical need today, along with future perspectives in this field.</p></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":"68 ","pages":"Article 102344"},"PeriodicalIF":4.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10834912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
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