Journal of receptor and signal transduction research最新文献_第2页

Identification of receptor-interacting protein kinase 3 inhibitor for atherosclerosis. 动脉粥样硬化受体相互作用蛋白激酶3抑制剂的鉴定。

IF 2.3

Journal of receptor and signal transduction research Pub Date : 2026-06-01 Epub Date: 2026-07-11 DOI: 10.1080/10799893.2026.2701222

Angneh Ngoruh, Ananya Anurag Anand, Rik Ganguly, Shashi Kumar Yadav, Prosperwell Ingty, Sintu Kumar Samanta, Atanu Bhattacharjee

{"title":"Identification of receptor-interacting protein kinase 3 inhibitor for atherosclerosis.","authors":"Angneh Ngoruh, Ananya Anurag Anand, Rik Ganguly, Shashi Kumar Yadav, Prosperwell Ingty, Sintu Kumar Samanta, Atanu Bhattacharjee","doi":"10.1080/10799893.2026.2701222","DOIUrl":"10.1080/10799893.2026.2701222","url":null,"abstract":"Cardiovascular diseases are the major cause of death worldwide. Atherosclerosis is a chronic inflammatory condition characterized by the accumulation of atherosclerotic plaques in the artery walls of medium and large arteries. Receptor-interacting protein kinase 3 (RIPK3) plays a major role in the development and instability of atherosclerotic plaque. Targeting RIPK3 is a promising therapeutic approach, as current inhibitors have reported side effects and lack specificity. In order to identify new and targeted RIPK3 inhibitors, this study focused on computational approach using methods such as virtual screening with essential descriptors such as drug-likeness and pharmacokinetic properties and docking studies. Three top compounds viz. ZINC96307758, ZINC96136342 and ZINC40012267 were identified that exhibit better binding scores compared to the reference inhibitor GSK843. Further analysis using density functional theory showed that the top compound was more reactive and stable compared to GSK843. The two complexes RIPK3-ZINC40012267 and RIPK3-ZINC96307758 showed the best stability, based on molecular dynamics simulations, as shown by its favorable free energy landscape and low RMSD and RMSF values. Strong binding free energy for the top hits was validated by MMPBSA calculations. Our results point to ZINC40012267 and ZINC96307758 as a particularly strong and stable RIPK3 inhibitor candidate, wet bench experimental validations are required to establish this finding.","PeriodicalId":520688,"journal":{"name":"Journal of receptor and signal transduction research","volume":" ","pages":"122-137"},"PeriodicalIF":2.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148428457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Computational design, synthesis, and in vitro evaluation of thiadiazole-derived PARP-1 inhibitors. 噻二唑类PARP-1抑制剂的计算设计、合成和体外评价。

IF 2.3

Journal of receptor and signal transduction research Pub Date : 2026-06-01 Epub Date: 2026-07-07 DOI: 10.1080/10799893.2026.2697740

Hardha Balachandran, Sowmiya Arun, Kaviarasan Lakshmanan, Dipen Purohit, Gowramma Byran, Kalirajan Rajagopal

{"title":"Computational design, synthesis, and in vitro evaluation of thiadiazole-derived PARP-1 inhibitors.","authors":"Hardha Balachandran, Sowmiya Arun, Kaviarasan Lakshmanan, Dipen Purohit, Gowramma Byran, Kalirajan Rajagopal","doi":"10.1080/10799893.2026.2697740","DOIUrl":"10.1080/10799893.2026.2697740","url":null,"abstract":"Background: Poly (ADP-ribose) polymerase-1 (PARP-1) is a crucial enzyme in DNA repair pathways and a significant target for cancer therapy. Due to their favorable physicochemical and biological characteristics, heterocyclic scaffolds like 1,3,4-thiadiazoles are good candidates for PARP-1 inhibitor design.Objectives: The purpose of this work was to use an integrated computational and experimental strategy to design, manufacture, and assess new 1,3,4-thiadiazole derivatives as possible PARP-1 inhibitors.Methods: MM-GBSA binding-energy calculations and molecular docking were used to create and screen a library of 1,3,4-thiadiazole analogues. Redocking the co-crystallized ligand confirmed the accuracy of the docking, resulting in an RMSD of 0.0000 Å. To evaluate drug-likeness and oral absorption characteristics, ADME predictions were made. The dynamic stability of the PARP-1-D1 complex was assessed using a 100-ns molecular dynamics simulation. The MTT assay was used to assess the in vitro cytotoxicity of the chosen compounds against MCF-7 cell lines.Results: Computational studies identified C10, D1, and E10 as the most promising PARP-1 inhibitors, showing strong binding through hydrophobic interactions, hydrogen bonds, and π-π stacking with key residues such as ARG878, ALA880, GLY894, TYR896, and SER864. ADME analysis indicated good physicochemical properties and oral availability. MD simulations confirmed the stability of the PARP-1-D1 complex. In vitro studies further validated their strong antiproliferative activity against MCF-7 cells.Conclusion: The combined computational and experimental results show that C10, D1, and E10 are promising lead scaffolds for the creation of new anticancer drugs that target PARP-1.","PeriodicalId":520688,"journal":{"name":"Journal of receptor and signal transduction research","volume":" ","pages":"100-112"},"PeriodicalIF":2.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148400115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effects of diffusion, affinity, and permeation rate on drug cell therapy. 扩散、亲和和渗透速率对药物细胞治疗的影响。

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Journal of receptor and signal transduction research Pub Date : 2026-06-01 Epub Date: 2026-07-10 DOI: 10.1080/10799893.2026.2699292

Terry Kenakin

引用次数: 0

Pharmacophore-based identification and molecular docking of CCR5 inhibitors: insights from dynamic simulations. 基于药效团的CCR5抑制剂鉴定和分子对接：来自动态模拟的见解。

IF 2.3

Journal of receptor and signal transduction research Pub Date : 2026-06-01 Epub Date: 2026-07-10 DOI: 10.1080/10799893.2026.2701217

Angadi Sathish Kumar, Estari Mamidala

{"title":"Pharmacophore-based identification and molecular docking of CCR5 inhibitors: insights from dynamic simulations.","authors":"Angadi Sathish Kumar, Estari Mamidala","doi":"10.1080/10799893.2026.2701217","DOIUrl":"10.1080/10799893.2026.2701217","url":null,"abstract":"The chemokine receptor type 5 (CCR5) plays a crucial role in HIV-1 entry into host cells, making it a key therapeutic target. This study aimed to identify novel CCR5 inhibitors through pharmacophore-guided virtual screening and molecular dynamics (MD) simulations using ZINC-derived compounds. The 3D structure of CCR5 (PDB ID: 4MBS) was used as the target receptor. A ligand-based pharmacophore model was generated using the Pharmit server, with Maraviroc as a reference molecule. Virtual screening of ZINC compounds was conducted based on pharmacophore features and Lipinski's Rule of Five. The top 10 compounds were subjected to molecular docking, ADMET analysis, and MD simulations using GROMACS to evaluate stability and binding dynamics. Among all screened ligands, ZINC000000867238 exhibited the strongest binding affinity (-10.0 kcal/mol), forming hydrogen bonds with Tyr251 and Glu283, and hydrophobic interactions with Trp86, Phe182, and Tyr108. The compound demonstrated favorable ADMET characteristics, including high absorption, non-mutagenicity, and absence of hERG inhibition. MD simulation confirmed its stability, with RMSD fluctuations between 0.20-0.38 nm, low RMSF deviations in active site residues, and a compact radius of gyration (∼2.48 nm) compared to apo-CCR5. The integrated computational approach identified ZINC000000867238 as a potent and stable CCR5 inhibitor candidate, warranting further in vitro and in vivo validation as a potential HIV-1 entry blocker.","PeriodicalId":520688,"journal":{"name":"Journal of receptor and signal transduction research","volume":" ","pages":"113-121"},"PeriodicalIF":2.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148428497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Molecular insights into voltage-gated sodium channels in excitable cells: pathophysiological roles and emerging therapeutic targets. 可兴奋细胞中电压门控钠通道的分子洞察：病理生理作用和新出现的治疗靶点。

IF 2.3

Journal of receptor and signal transduction research Pub Date : 2026-04-01 Epub Date: 2026-06-01 DOI: 10.1080/10799893.2026.2676552

Akash Vikal, Rashmi Maurya, Pradeep Kumar, Navneet Verma, Arun Kumar Mishra

{"title":"Molecular insights into voltage-gated sodium channels in excitable cells: pathophysiological roles and emerging therapeutic targets.","authors":"Akash Vikal, Rashmi Maurya, Pradeep Kumar, Navneet Verma, Arun Kumar Mishra","doi":"10.1080/10799893.2026.2676552","DOIUrl":"10.1080/10799893.2026.2676552","url":null,"abstract":"Voltage-gated sodium channels (VGSCs; Nav1.1-Nav1.9) are necessary for the initiation and propagation of action potentials in neurons, cardiac muscle and skeletal muscle. Because of their functional importance, VGSCs have become promising candidates for drug development in the brain, heart, and pain. The aim of this review is to highlight the structure, physiological role and pathological involvement of VGSCs in several different diseases, such as epilepsy, arrhythmias, chronic pain and cancer. Clinically established VGSC-targeting drugs are discussed, as well as recent evidence that shows an involvement of VGSCs in tumor progression and metastasis. Lack of selectivity, blood-brain barrier penetration, and regulatory complexities are among the challenges faced by VGSC-targeted therapy, as discussed in the review. Other challenges with VGSC-targeted therapy, such as high isoform homology, limited selectivity, blood-brain barrier penetration, and regulatory complexities, are also discussed in the review. In addition, new isoform-specific modulation strategies, innovative drug delivery devices, and new therapeutic approaches are highlighted. In summary, VGSCs are interesting but complex therapeutic targets, and future progress in selective targeting and drug delivery will likely increase their potential use across a variety of neurological, cardiovascular, and oncological disorders.","PeriodicalId":520688,"journal":{"name":"Journal of receptor and signal transduction research","volume":" ","pages":"66-76"},"PeriodicalIF":2.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148140234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeting vascular endothelial growth factor and its receptors in non-small cell lung cancer for improved treatment strategies. 靶向血管内皮生长因子及其受体治疗非小细胞肺癌

IF 2.3

Journal of receptor and signal transduction research Pub Date : 2026-04-01 Epub Date: 2026-03-12 DOI: 10.1080/10799893.2026.2639309

Rajesh B Nanaware, Anuruddha R Chabukswar, Priyanka S Waghmare, Swati C Jagdale

{"title":"Targeting vascular endothelial growth factor and its receptors in non-small cell lung cancer for improved treatment strategies.","authors":"Rajesh B Nanaware, Anuruddha R Chabukswar, Priyanka S Waghmare, Swati C Jagdale","doi":"10.1080/10799893.2026.2639309","DOIUrl":"10.1080/10799893.2026.2639309","url":null,"abstract":"Non-small cell lung cancer (NSCLC) is responsible for about 85% of all lung cancers and is a major contributor to cancer deaths worldwide. Angiogenesis, mainly mediated by vascular endothelial growth factor (VEGF) and its receptors (VEGFRs), is a key factor involved in the progression and metastasis of NSCLCs and the development of drug resistance. Anti-angiogenic therapy, for instance, with monoclonal antibodies like bevacizumab and ramucirumab, as well as multi-targeted tyrosine kinase inhibitors (TKIs) like nintedanib and anlotinib has been shown to improve the management of NSCLC. Despite the improvement in the management, patients develop resistance through mechanisms such as hypoxia signaling, alternative angiogenic factor activation, vascular structure remodeling, and a suppressive tumor microenvironment (TME). Recent studies have revealed the use of a combination of anti-angiogenic therapy and immune checkpoint blockade to normalize the tumor vasculature, thus enhancing treatment efficacy. Angiogenesis-associated biomarkers, despite extensive research, have not been seen to have a clinical impact in the management and treatment of NSCLC because of the heterogeneous characteristics and the dynamic regulation of the cascade. This review summarizes current VEGF/VEGFR-targeted therapies in NSCLC, mechanisms of resistance, and future directions toward biomarker-guided therapeutic optimization.","PeriodicalId":520688,"journal":{"name":"Journal of receptor and signal transduction research","volume":" ","pages":"47-57"},"PeriodicalIF":2.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147438891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

β₁/β₂ adrenergic dysregulation: a missing link between mitochondrial fission/fusion in the failing heart. β1/β2肾上腺素能失调：衰竭心脏中线粒体裂变/融合之间的缺失环节。

IF 2.3

Journal of receptor and signal transduction research Pub Date : 2026-04-01 Epub Date: 2026-04-08 DOI: 10.1080/10799893.2026.2652855

Pranav Panchbhai, Gauri Chaturvedi, Satnam Singh, Nandini Dubey, Rajiv Narang, Neeraj Parakh, Prabhakar Singh, Upendra Baitha, Ved Prakash, Harlokesh Narayan Yadav

{"title":"β1/β2 adrenergic dysregulation: a missing link between mitochondrial fission/fusion in the failing heart.","authors":"Pranav Panchbhai, Gauri Chaturvedi, Satnam Singh, Nandini Dubey, Rajiv Narang, Neeraj Parakh, Prabhakar Singh, Upendra Baitha, Ved Prakash, Harlokesh Narayan Yadav","doi":"10.1080/10799893.2026.2652855","DOIUrl":"10.1080/10799893.2026.2652855","url":null,"abstract":"Heart failure (HF) is characterized by notable alterations in β-adrenergic receptor (β-AR) signaling. It is well known that a prolonged overstimulation of β-ARs, a member of the G-protein-coupled receptor (GPCR) family, alters receptor density and function, contributing to cardiac dysfunction and the development and progression of HF. Moreover, recently, many studies have highlighted the role of β-ARs in the regulation of mitochondrial fission/fusion. A dysfunctional mitochondrial fission/fusion balance is a characteristic hallmark of a failing heart. However, a mechanistic link between β-ARs and mitochondrial dynamics is lacking. Furthermore, growing evidence links β-AR activity to changing mitochondrial size, distribution, and functional integrity. Yet these findings remain scattered across diverse studies with differing perspectives. This review demonstrates a clear mechanistic view of β-ARs regulation of mitochondrial fission/fusion in a failing heart.","PeriodicalId":520688,"journal":{"name":"Journal of receptor and signal transduction research","volume":" ","pages":"58-65"},"PeriodicalIF":2.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147635658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Discrepancies in β-adrenergic receptor signaling and cAMP pathway in high-fat simple carbohydrate diet-fed C57BL/6J mice: implications for metabolic syndrome pathophysiology. 高脂单糖饮食C57BL/6J小鼠β-肾上腺素能受体信号和cAMP通路的差异：对代谢综合征病理生理的影响

IF 2.3

Journal of receptor and signal transduction research Pub Date : 2026-02-01 Epub Date: 2026-02-11 DOI: 10.1080/10799893.2026.2625468

Vijayalakshmi Gangadhara, Kavishankar Gawli, Asha Abraham

{"title":"Discrepancies in β-adrenergic receptor signaling and cAMP pathway in high-fat simple carbohydrate diet-fed C57BL/6J mice: implications for metabolic syndrome pathophysiology.","authors":"Vijayalakshmi Gangadhara, Kavishankar Gawli, Asha Abraham","doi":"10.1080/10799893.2026.2625468","DOIUrl":"10.1080/10799893.2026.2625468","url":null,"abstract":"The regulation of beta-adrenergic receptors (β-ARs) is crucial for maintaining pancreatic function and metabolic balance. However, the rising incidence of metabolic syndrome (MetS) highlights the need to understand how a high-fat simple carbohydrate (HFSC) diet affects β-AR signaling in the pancreas. Despite its potential significance, this aspect remains underexplored. We hypothesized that MetS-induced alterations in β-AR subtypes may disrupt regulatory mechanisms, potentially affecting adenylate cyclase coupling. This study investigated the impact of an HFSC diet on β-AR subtype expression and downstream signaling in pancreatic islets. MetS was induced in C57BL/6J mice through a 150-day HFSC diet. Metabolic changes were assessed through anthropometric parameters, blood glucose levels, lipid profiles, and pancreatic islet morphology. β-AR subtype expression (Adrb1/ADRB1, Adrb2/ADRB2, Adrb3/ADRB3), cAMP levels, and receptor localization were evaluated using quantitative real-time PCR (qRT-PCR), Western blotting, and immunofluorescence. The HFSC diet led to metabolic disturbances and pancreatic inflammation. Adrb1 mRNA expression was elevated (p < 0.001), but β1-AR localization did not show a corresponding increase. Both β2-AR transcription and translation were downregulated (p < 0.001). Although β3-AR protein levels were markedly increased (p < 0.001), cAMP levels were significantly reduced (p < 0.01). These findings indicate significant β-AR dysregulation under metabolic stress. Altered β1-AR and β2-AR expression, along with increased but functionally insufficient β3-AR signaling, suggest impaired adrenergic regulation in pancreatic islets during MetS. This study contributes to understanding MetS pathophysiology and highlights the relevance of β-AR signaling as a potential therapeutic target.","PeriodicalId":520688,"journal":{"name":"Journal of receptor and signal transduction research","volume":" ","pages":"36-46"},"PeriodicalIF":2.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146169243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Signaling complexity in diabetic neuropathy: a multitargeted perspective on pathogenesis and therapy. 糖尿病神经病变的信号复杂性：发病机制和治疗的多靶点视角。

IF 2.3

Journal of receptor and signal transduction research Pub Date : 2026-02-01 Epub Date: 2025-12-21 DOI: 10.1080/10799893.2025.2603983

Tanya Gupta, Thakur Gurjeet Singh, Randhir Singh

{"title":"Signaling complexity in diabetic neuropathy: a multitargeted perspective on pathogenesis and therapy.","authors":"Tanya Gupta, Thakur Gurjeet Singh, Randhir Singh","doi":"10.1080/10799893.2025.2603983","DOIUrl":"10.1080/10799893.2025.2603983","url":null,"abstract":"Diabetic neuropathy (DN), a prevalent and disabling complication of diabetes mellitus is characterized by chronic pain, sensory loss, and motor impairment arising from multifaceted metabolic, inflammatory, and oxidative mechanisms triggered by chronic hyperglycemia. Among the metabolic contributors, polyol pathway, AGE, PKC pathway, and hexosamine biosynthetic pathway are key players. These are closely intertwined with inflammatory mediators and pathways, including NF-κB, MAPK, the NLRP3 inflammasome, cytokine/chemokine signaling, and emerging inflammatory circuits. Mitochondrial dysfunction and oxidative stress, exacerbated by the impairment of AMPK/SIRT/PGC-1α and Nrf2 signaling, contribute to cellular damage and bioenergetic failure. Additionally, disruptions in insulin signaling, specifically involving Akt and RAC1 pathways, worsen neuronal survival, cytoskeletal function, and glucose metabolism. The interplay between these pathways establishes a self-propagating cycle of metabolic stress, inflammation, and neurodegeneration. Recent research has focused on targeting these specific mechanisms, including aldose reductase inhibitors, RAGE antagonists, PKC inhibitors, AMPK activators, and Nrf2 inducers. While many have shown promise in preclinical models, clinical translation remains limited. Understanding the intricate crosstalk between these pathways is essential for developing more effective, multi-targeted interventions aimed at halting or reversing the progression of DN. This review explores the multifaceted pathways underlying DN, including metabolic, inflammatory, mitochondrial dysfunction, and insulin signaling pathways. It highlights the intricate interlinks between these mechanisms and discusses recent advancements in targeted therapeutic approaches.","PeriodicalId":520688,"journal":{"name":"Journal of receptor and signal transduction research","volume":" ","pages":"1-14"},"PeriodicalIF":2.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145800958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","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 selective U-II receptor antagonists in modifying vascular function in intact and denuded aortic diabetic rats. 选择性U-II受体拮抗剂在改变完整和剥脱主动脉糖尿病大鼠血管功能中的作用。

IF 2.3

Journal of receptor and signal transduction research Pub Date : 2026-02-01 Epub Date: 2026-01-11 DOI: 10.1080/10799893.2026.2613868

Sonia Sh Abdulfatah, Ridha H Hussein

{"title":"Role of selective U-II receptor antagonists in modifying vascular function in intact and denuded aortic diabetic rats.","authors":"Sonia Sh Abdulfatah, Ridha H Hussein","doi":"10.1080/10799893.2026.2613868","DOIUrl":"10.1080/10799893.2026.2613868","url":null,"abstract":"Background: Urotensin-II (U-II) is a potent vasoconstrictor acting via UT receptors. Endothelial buffering normally restrains U-II signaling, but this protection is diminished in diabetes mellitus, contributing to vascular dysfunction. Selective UT antagonists such as Urantide (peptidic) and Palosuran (non-peptidic) are promising, yet direct comparisons under diabetic conditions remain limited.Objective: To assess the effects of Urantide and Palosuran on U-II-induced vasoconstriction in aortae from non-diabetic and diabetic rats with intact and denuded endothelium.Methods: Thoracic aortic rings were mounted for isometric recording. Concentration-response curves to U-II (<math><mrow><msup><mrow><mn>10</mn></mrow><mrow><mo>-</mo><mn>11</mn></mrow></msup></mrow></math>-<math><mrow><msup><mrow><mn>10</mn></mrow><mrow><mo>-</mo><mn>8</mn></mrow></msup></mrow></math> M) were generated in the presence or absence of Urantide or Palosuran (1 µM).Results: Endothelial loss nearly doubled U-II contractions in non-diabetic aorta and unmasked hyperreactivity in diabetic vessels. Urantide abolished efficacy, while Palosuran attenuated both efficacy and potency, with pronounced inhibition in diabetic denuded rings.Conclusion: UT antagonism effectively suppresses U-II reactivity through distinct pharmacological profiles, highlighting therapeutic potential in diabetic vasculopathy.","PeriodicalId":520688,"journal":{"name":"Journal of receptor and signal transduction research","volume":" ","pages":"28-35"},"PeriodicalIF":2.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145954922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0