Pharmacology Research & Perspectives最新文献_第4页

Assessments of CYP-Inhibition-Based Drug-Drug Interactions Between Tofacitinib and Lipid-Lowering Agents in Rats Both In Vitro and In Vivo. 体外和体内大鼠托法替尼与降脂剂之间基于cep抑制的药物-药物相互作用的评估。

IF 2.9 4区医学

Pharmacology Research & Perspectives Pub Date : 2025-06-01 DOI: 10.1002/prp2.70127

Hang Yang, Shuanghu Wang, Quan Zhou, Peiwu Geng, Zebei Lu, Qinrong Lin, Chunhong Chen, Yunfang Zhou, Jianping Cai, Dapeng Dai

{"title":"Assessments of CYP-Inhibition-Based Drug-Drug Interactions Between Tofacitinib and Lipid-Lowering Agents in Rats Both In Vitro and In Vivo.","authors":"Hang Yang, Shuanghu Wang, Quan Zhou, Peiwu Geng, Zebei Lu, Qinrong Lin, Chunhong Chen, Yunfang Zhou, Jianping Cai, Dapeng Dai","doi":"10.1002/prp2.70127","DOIUrl":"10.1002/prp2.70127","url":null,"abstract":"Tofacitinib is a widely used medication for the treatment of arthritis. It has been reported that some patients experience abnormal cholesterol levels following treatment, leading to recommendations for the coadministration of lipid-lowering drugs such as statins. In this study, we investigated the potential drug-drug interactions between tofacitinib and the statins simvastatin and lovastatin. In the in vitro experiments, rat liver microsomes were employed to evaluate the inhibitory effects of lipid-lowering agents on the metabolism of tofacitinib, with the primary metabolite M8 analyzed using ultra-performance liquid chromatography-tandem mass spectrometry. The results showed that simvastatin and lovastatin significantly inhibited the metabolism of tofacitinib, with IC50 values of 5.837 and 10.68 μM, respectively. For the in vivo pharmacokinetic studies, Sprague-Dawley rats were pretreated with simvastatin or lovastatin via oral gavage for 7 days before the oral gavage of tofacitinib. This pretreatment led to an increased area under the concentration-time curve of tofacitinib, suggesting that a potential reduction in the first metabolism and/or systemic clearance takes place. These findings demonstrate significant interactions between tofacitinib and certain lipid-lowering agents in the rat model, particularly simvastatin and lovastatin, both in vitro and in vivo.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 3","pages":"e70127"},"PeriodicalIF":2.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12124994/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144192122","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

Monitoring Serum Bisoprolol Concentrations in Patients With Heart Failure With Reduced Ejection Fraction: Results of a Pilot Study From Routine Health Care. 监测心力衰竭伴射血分数降低患者的血清比索洛尔浓度：一项来自常规医疗保健的初步研究结果。

IF 2.3 4区医学

Pharmacology Research & Perspectives Pub Date : 2025-06-01 DOI: 10.1002/prp2.70089

Ivana Kacirova, Marie Lazarova, Romana Urinovska, Jozef Dodulik, Diana Drienikova, Jan Vaclavik

{"title":"Monitoring Serum Bisoprolol Concentrations in Patients With Heart Failure With Reduced Ejection Fraction: Results of a Pilot Study From Routine Health Care.","authors":"Ivana Kacirova, Marie Lazarova, Romana Urinovska, Jozef Dodulik, Diana Drienikova, Jan Vaclavik","doi":"10.1002/prp2.70089","DOIUrl":"10.1002/prp2.70089","url":null,"abstract":"Bisoprolol is a second-generation, highly selective beta-1 adrenergic receptor antagonist with various beneficial effects in patients with heart failure. Interindividual variability in response to bisoprolol is known, and finding the optimal dose for individual patients with heart failure is still challenging. This pilot study included patients treated with bisoprolol for chronic heart failure with reduced ejection fraction. Between November 2022 and November 2023, one to six blood samples were collected from these patients to determine the trough serum concentration of bisoprolol. At the same time, the values of selected clinical variables were recorded. Bisoprolol concentrations ranged from 1.1 to 65.0 μg/L and correlated with both the daily dose and the dose per kilogram of body weight. However, wide variability in measured serum concentrations of bisoprolol was observed at the same daily dose and in apparent weight-adjusted clearance. Patients classified as NYHA III-IV received a 33% higher dose per kilogram of body weight than patients in NYHA I-II but achieved 165% higher serum concentrations of bisoprolol. An inverse correlation was found between diastolic blood pressure and dose per kilogram of body weight, and a positive correlation between N-terminal pro-B-type natriuretic peptide and both dose per kilogram of body weight and serum bisoprolol concentration. A wide variability in patients' serum concentrations of bisoprolol achieved after taking the same dose has been observed. A significantly higher concentration-to-dose ratio and a significantly lower weight-adjusted apparent clearance were demonstrated in patients with reduced cardiac function, reduced renal function, and taking the combination with amiodarone. These patients may be more prone to overdose with bisoprolol.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 3","pages":"e70089"},"PeriodicalIF":2.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12033214/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144039238","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

Accounting for Time-Varying Confounding in a Self-Controlled Case Series of Fluoroquinolone Treatment for Uncomplicated Urinary Tract Infections and Risk of Collagen-Related Events. 氟喹诺酮类药物治疗无并发症尿路感染和胶原蛋白相关事件风险自控病例系列的时变混杂因素分析

IF 2.3 4区医学

Pharmacology Research & Perspectives Pub Date : 2025-06-01 DOI: 10.1002/prp2.70124

Anna Schultze, Shinyoung Ju, Myriam Drysdale, George Mu, Fanny S Mitrani-Gold, John Logie

{"title":"Accounting for Time-Varying Confounding in a Self-Controlled Case Series of Fluoroquinolone Treatment for Uncomplicated Urinary Tract Infections and Risk of Collagen-Related Events.","authors":"Anna Schultze, Shinyoung Ju, Myriam Drysdale, George Mu, Fanny S Mitrani-Gold, John Logie","doi":"10.1002/prp2.70124","DOIUrl":"10.1002/prp2.70124","url":null,"abstract":"We report findings from three SCCS conducted to quantify the association between fluoroquinolone (FQ) use for the treatment of uncomplicated urinary tract infection (uUTI) and tendon rupture, retinal detachment, and uveitis. Female patients aged ≥ 12 years old in the Optum Clinformatics Data Mart database with an outcome of interest and exposure to either oral FQ or trimethoprim/sulfamethoxazole (SXT) in the 5 days following a newly reported uUTI during the study period (01/01/2011-02/10/2019) were included. We considered a 90-day risk window for each outcome following drug exposure. Incidence rate ratios (IRR) and 95% confidence intervals (CI) were estimated using conditional Poisson regression, adjusting for age and calendar time, incorporating SXT as an active comparator. We found little evidence of an association between FQ use compared to SXT and any of the outcomes of interest (tendon rupture: IRR = 1.01, 95% CI = 0.91-1.21; retinal detachment: IRR = 0.99, 95% CI = 0.86-1.14; and uveitis: IRR = 1.09, 95% CI = 0.97-1.22). Incorporating the active comparator using two different methods did not change conclusions. The lack of evidence for an association between short-term use of FQ and the comparator antibiotic (SXT) for the treatment of uUTI and collagen-related events also implies that there was no marked association between uUTI and these outcomes. However, power was limited, and a small increased risk cannot be ruled out. Using active comparators in SCCS can improve the robustness of studies of antibiotics and adverse events.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 3","pages":"e70124"},"PeriodicalIF":2.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12093150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111598","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

Pharmacogenetic Study of Anti-TB Drugs in the Native Ancestry Peruvian Population. 秘鲁土著祖先人群抗结核药物的药理学研究。

IF 2.9 4区医学

Pharmacology Research & Perspectives Pub Date : 2025-06-01 DOI: 10.1002/prp2.70135

Luis Jaramillo-Valverde, Mary K Horton, Julio A Poterico, Cristina M Lanata, Heinner Guio

{"title":"Pharmacogenetic Study of Anti-TB Drugs in the Native Ancestry Peruvian Population.","authors":"Luis Jaramillo-Valverde, Mary K Horton, Julio A Poterico, Cristina M Lanata, Heinner Guio","doi":"10.1002/prp2.70135","DOIUrl":"10.1002/prp2.70135","url":null,"abstract":"In Peru, 33 113 individuals were diagnosed with tuberculosis (TB) in 2023. While TB treatments are generally effective, 3.4% to 13% of cases are associated with significant adverse drug reactions, with drug-induced liver injury (DILI) being the most prevalent. Limited data exist on genetic risk factors for DILI in Latin America; even less is known about these factors in native Peruvian populations. This study aimed to determine the prevalence of TB drug-metabolizing genotypes in these populations. A cross-sectional analysis was conducted using genetic data from 254 participants from the Peruvian Genome Project (PGP) representing three subpopulations: Coast, Andes, and Amazon. Twenty-three genes associated with TB treatment, include isoniazid, rifampin, ethambutol, and pyrazinamide, as identified in the PharmGKB database, were analyzed. Significant differences were observed in genotype frequencies among subpopulations for AGBL4, NAT2, GSTP1, SLCO1B1, NOS, and CYP2B6 genes. The Amazonian population demonstrated a higher risk of DILI due to the increased prevalence of hepatotoxic alleles in AGBL4, GSTP1, and SLCO1B1. In contrast, alleles in the NOS gene indicated a lower risk of hepatotoxicity in the Andean population. However, the high-risk genotypes identified in the study's native Peruvian populations exhibit distinct prevalence patterns compared to those reported in the 1000 Genomes Project. These findings can inform the development of personalized therapeutic strategies to improve TB treatment outcomes among Peru's diverse subpopulations.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 3","pages":"e70135"},"PeriodicalIF":2.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12167507/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302708","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

Psychotropic Polypharmacy and QT Prolonging Medications in Hospitalized Patients. 住院患者的精神药物综合用药和QT延长药物。

IF 2.9 4区医学

Pharmacology Research & Perspectives Pub Date : 2025-06-01 DOI: 10.1002/prp2.70107

Joel Moore, Isabella Singh, Ruby Tszwai Au, Genevieve Gabb, Joanne Eng-Frost, Elizabeth Hotham, Sepehr Shakib, Vijayaprakash Suppiah

{"title":"Psychotropic Polypharmacy and QT Prolonging Medications in Hospitalized Patients.","authors":"Joel Moore, Isabella Singh, Ruby Tszwai Au, Genevieve Gabb, Joanne Eng-Frost, Elizabeth Hotham, Sepehr Shakib, Vijayaprakash Suppiah","doi":"10.1002/prp2.70107","DOIUrl":"10.1002/prp2.70107","url":null,"abstract":"It is common for patients with mental illnesses to be prescribed multiple psychotropic medications to effectively manage their conditions. Psychotropic polypharmacy has been shown to potentiate and increase the risks of several adverse effects, including QT prolongation. This study aimed to investigate the prescribing trends of and differences in prescribing of QT-prolonging medications (QTPMs) at admission and discharge in hospitalized patients. This retrospective observational study utilized inpatient data from three public hospitals between January and December 2019. QTPMs were classified according to the AZCERT classification. QTPMs doses were evaluated by calculating the ratio of prescribed daily dose (PDD) to the defined daily dose (DDD). Subgroup analyses showed significant differences between patient groups on admission and discharge (all p < 0.001). Mean QTPMs decreased significantly between the two time points only in patients admitted to acute medical and geriatric units (p < 0.001). PDD/DDD ratio for conditional risk QTPMs in acute mental health unit (AMHU) patients was increased at discharge (p = 0.038). Patients admitted to acute medical and geriatric units were four and eight times more likely to be discharged with one QTPM with known risk in combination with more QTPMs with conditional risk. Logistic regression showed significant relationships with age and total number of regular medicines at admission for those prescribed high-dose QTPMs at discharge. The findings underscore the necessity for enhanced monitoring of QTPMs in hospitalized patients, particularly for those at higher risk.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 3","pages":"e70107"},"PeriodicalIF":2.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12041124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144047832","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

Rapidly Polymerizing Click Hydrogel Provides Localized Delivery of rhBMP2 to Promote Bone Formation. 快速聚合Click水凝胶提供rhBMP2的局部递送促进骨形成。

IF 2.9 4区医学

Pharmacology Research & Perspectives Pub Date : 2025-06-01 DOI: 10.1002/prp2.70119

D Joshua Cohen, Thomas W Jacobs, D Scott Wilson, Michael C Mancini, Christine Van Duyn, Zvi Schwartz, Barbara D Boyan

{"title":"Rapidly Polymerizing Click Hydrogel Provides Localized Delivery of rhBMP2 to Promote Bone Formation.","authors":"D Joshua Cohen, Thomas W Jacobs, D Scott Wilson, Michael C Mancini, Christine Van Duyn, Zvi Schwartz, Barbara D Boyan","doi":"10.1002/prp2.70119","DOIUrl":"10.1002/prp2.70119","url":null,"abstract":"Delivery of bioactive agents to achieve tissue regeneration at targeted sites with minimal side effects requires the use of biodegradable carriers and sustained release of the therapeutic at appropriate concentrations. We developed a copper-free polyethylene glycol-based click hydrogel to deliver bone morphogenetic protein-2 (BMP2), a potent regulator for bone regeneration that is currently delivered to orthotopic sites using an absorbable collagen sponge, leading to a burst release of BMP2, potentially causing ectopic bone formation. In contrast, the hydrogel is delivered as a liquid, conforming to the contours of treatment sites, polymerizing rapidly at body temperature without generating heat, exhibiting minimal swelling after gelation, and releasing its payload as it degrades. We assessed the safety and effectiveness of BMP2 delivery in vitro and in mouse cranial defects in vivo, comparing it to BMP2 delivered via a collagen sponge. No toxicity was observed in vitro or systemically, nor was there allergic sensitization caused by the hydrogel in rabbits. Released BMP2 increased the production of osteogenic markers in vitro. Hydrogel + BMP2 caused equivalent defect closure and total bone growth compared to collagen + BMP2; however, there was more vascularization within the defect but less bone growth outside of the defect on the calvaria for hydrogel + BMP2 compared to collagen + BMP2. In conclusion, the click hydrogels used in this study are safe and effective for administering BMP2 with fewer undesired off-target effects and high potential to be used with BMP2 for bone regeneration, supporting the use of click chemistry hydrogels to deliver bioactive agents to treatment sites safely and effectively.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 3","pages":"e70119"},"PeriodicalIF":2.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12146212/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144249143","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

National Granted Programs and Public Funds for Biopharmaceutical Startups in Japan. 日本生物制药初创企业的国家资助计划和公共基金。

IF 2.3 4区医学

Pharmacology Research & Perspectives Pub Date : 2025-06-01 DOI: 10.1002/prp2.70106

Ryo Okuyama

{"title":"National Granted Programs and Public Funds for Biopharmaceutical Startups in Japan.","authors":"Ryo Okuyama","doi":"10.1002/prp2.70106","DOIUrl":"10.1002/prp2.70106","url":null,"abstract":"In Japan, biopharmaceutical startups have not been sufficiently nurtured, leading to weak international competitiveness in new drug development. This is partly due to low levels of entrepreneurship in the private sector and limited investment in startups. Therefore, it is crucial for the Japanese government to provide financial support for biopharmaceutical startups. This study aims to offer a comprehensive overview of the current state of government grants and investments for biopharmaceutical startups in Japan, as well as to discuss the associated challenges and future directions. Both grant programs specifically focused on drug discovery and development and those supporting a broader range of industries, including drug discovery and development, were identified through literature reviews and web searches. Advisory programs affiliated with government agencies that assist biopharmaceutical startups were also identified. Additionally, the government has established national university funds at four universities, which have made investments in biopharmaceutical startups. While the government offers various grant programs to support biopharmaceutical startups at different stages of research and development, the relatively small scale of these grants and limited support for seed-stage projects pose significant challenges. Consulting services provided by the government, which offer advice on drug development strategies and processes, have been particularly beneficial for university researchers in Japan who lack expertise in drug discovery and development. However, some initiatives spread across different ministries, highlighting the need for a more unified national approach.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 3","pages":"e70106"},"PeriodicalIF":2.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12034747/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144036720","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

In Vitro Signaling Properties of Cannabinoid and Orexin Receptors: How Orexin Receptors Influence Cannabinoid Receptor-Mediated Signaling. 大麻素和食欲素受体的体外信号特性：食欲素受体如何影响大麻素受体介导的信号传导。

IF 2.9 4区医学

Pharmacology Research & Perspectives Pub Date : 2025-04-01 DOI: 10.1002/prp2.70078

Kawthar A Mohamed, Robert B Laprairie

{"title":"In Vitro Signaling Properties of Cannabinoid and Orexin Receptors: How Orexin Receptors Influence Cannabinoid Receptor-Mediated Signaling.","authors":"Kawthar A Mohamed, Robert B Laprairie","doi":"10.1002/prp2.70078","DOIUrl":"10.1002/prp2.70078","url":null,"abstract":"The co-expression of different types of G protein-coupled receptors (GPCRs) in the same cells can have implications for receptor signaling and receptor cross-talk, potentially altering the apparent potency or efficacy of ligands targeting each receptor. The endocannabinoid and orexinergic systems, consisting of class A GPCRs and their endogenous ligands, are highly complex and regulate processes such as appetite, sleep, nociception, and energy homeostasis. The shared anatomical distribution of cannabinoid and orexin receptors in various regions of the central nervous system (CNS), coupled with data from previous studies exploring physical and functional interactions between these receptors, suggests that the endocannabinoid and orexinergic systems engage in crosstalk. In this study, we explored how orexin receptors (OX1, OX2) altered the in vitro signaling of cannabinoid receptors (CB1, CB2) in Chinese hamster ovary (CHO)-K1 cells by quantifying cyclic adenosine monophosphate (cAMP) inhibition and βarrestin2 recruitment. Our results suggest that orexin receptors alter agonist-dependent signaling at the cannabinoid receptors by enhancing cannabinoid receptor-mediated cAMP inhibition while increasing or decreasing cannabinoid receptor-mediated βarrestin2 recruitment. These initial results are important for understanding the effects associated with cannabinoid ligands and may provide novel insights for therapeutics targeting physiological processes modulated by both systems.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 2","pages":"e70078"},"PeriodicalIF":2.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11860274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143503191","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

The Chicken Embryo: An Alternative Animal Model in Development, Disease and Pharmacological Treatment. 鸡胚：一种发育、疾病和药理治疗的替代动物模型。

IF 2.9 4区医学

Pharmacology Research & Perspectives Pub Date : 2025-04-01 DOI: 10.1002/prp2.70086

Oykum Kaplan-Arabaci, Zuzana Dančišinová, Ragnhild Elisabeth Paulsen

{"title":"The Chicken Embryo: An Alternative Animal Model in Development, Disease and Pharmacological Treatment.","authors":"Oykum Kaplan-Arabaci, Zuzana Dančišinová, Ragnhild Elisabeth Paulsen","doi":"10.1002/prp2.70086","DOIUrl":"10.1002/prp2.70086","url":null,"abstract":"To examine various medications and substances, in vivo models such as rats and mice are routinely used. However, it is utterly desirable to reduce extensive amounts of animals for these experimental models, which are costly and time-consuming. Animals are frequently put through a variety of procedures that could cause them pain, distress, or even harm; therefore, it is important to think about the ethical ramifications of using them in research. Thus, by following the three R's of animal research: reduction, replacement, and refinement, living animals used in studies should be minimized. The embryo of Gallus gallus, the domestic chicken, is a great model to research many different diseases and conditions. Its efficient blood supply from the chorioallantoic membrane gives us a unique possibility to administer chemicals or cells to the embryo in a noninvasive manner. In this review, we evaluate some advantages and disadvantages of using the developing chicken as an alternative in vivo model for development, disease, and pharmacological treatment. We focus on the top two leading causes of death: neurological disorders and cancer. We present a number of studies that describe the use of the chicken embryo in neuroscience and neurodevelopment research, in cancer research, and pharmacodynamic and pharmacokinetic studies. These studies show that the chicken embryo is an inexpensive, readily available, self-sufficient model with a short incubation period, high accessibility, and ideal for drug screening, making it an appealing model that can provide insightful biological and pharmacological information.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 2","pages":"e70086"},"PeriodicalIF":2.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11925699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670453","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

β-Adrenergic Blockers Increase cAMP and Stimulate Insulin Secretion Through a PKA/RYR2/TRPM5 Pathway in Pancreatic β-Cells In Vitro. β-肾上腺素能阻滞剂通过PKA/RYR2/TRPM5途径增加胰腺β-细胞cAMP并刺激胰岛素分泌

IF 2.9 4区医学

Pharmacology Research & Perspectives Pub Date : 2025-04-01 DOI: 10.1002/prp2.70092

Naoya Murao, Risa Morikawa, Yusuke Seino, Kenju Shimomura, Yuko Maejima, Yuichiro Yamada, Atsushi Suzuki

{"title":"β-Adrenergic Blockers Increase cAMP and Stimulate Insulin Secretion Through a PKA/RYR2/TRPM5 Pathway in Pancreatic β-Cells In Vitro.","authors":"Naoya Murao, Risa Morikawa, Yusuke Seino, Kenju Shimomura, Yuko Maejima, Yuichiro Yamada, Atsushi Suzuki","doi":"10.1002/prp2.70092","DOIUrl":"https://doi.org/10.1002/prp2.70092","url":null,"abstract":"β-adrenergic blockers (β-blockers) are extensively used to inhibit β-adrenoceptor activation and subsequent cAMP production in many cell types. In this study, we characterized the effects of β-blockers on mouse pancreatic β-cells. Unexpectedly, high concentrations (100 μM) of β-blockers (propranolol and bisoprolol) paradoxically increased cAMP levels 5-10 fold, enhanced Ca2+ influx, and stimulated a 2-4 fold increase in glucose- and glimepiride-induced insulin secretion in MIN6-K8 clonal β-cells and isolated mouse pancreatic islets. These effects were observed despite minimal expression of β-adrenoceptors in these cells. Mechanistically, the cAMP increase led to ryanodine receptor 2 (RYR2) phosphorylation via protein kinase A (PKA), triggering Ca2+-induced Ca2+ release (CICR). CICR then activates transient receptor potential cation channel subfamily M member 5 (TRPM5), resulting in increased Ca2+ influx via voltage-dependent Ca2+ channels. These effects contradict the conventional understanding of the pharmacology of β-blockers, highlighting the variability in β-blocker actions depending on the experimental context.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 2","pages":"e70092"},"PeriodicalIF":2.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11994265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144010766","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