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British Journal of Pharmacology

Kirin Gada, Leigh D Plant
Chronic pain is a debilitating and increasingly common medical problem with few effective treatments. In addition to the direct and indirect economic burden of pain syndromes, the concomitant increase in prescriptions for narcotics has contributed to a sharp rise in deaths associated with drug misuse-the 'opioid crisis'. Together, these issues highlight the unmet clinical and social need for a new generation of safe, efficacious analgesics. The detection and transmission of pain stimuli is largely mediated by somatosensory afferent fibres of the dorsal root ganglia...
October 16, 2018: British Journal of Pharmacology
Jun Fan, Di Li, Hong-Sheng Chen, Jian-Geng Huang, Jun-Feng Xu, Wen-Wen Zhu, Jian-Guo Chen, Fang Wang
BACKGROUND AND PURPOSE: Altered function or expression of gamma aminobutyric acid type A receptors (GABAA Rs) contribute to anxiety disorders. Benzodiazepines (BZDs) are widely prescribed for the treatment of anxiety. However, the long-term use of BZDs has been shown to increase the risk of developing drug dependence and tolerance. Thus, it is urgent to explore new therapeutic approaches. Metformin is widely used to treat type II diabetes and other metabolic syndromes. However, the role of metformin in psychiatric disorders, especially anxiety remains largely unknown...
October 14, 2018: British Journal of Pharmacology
Christopher Schultz
No abstract text is available yet for this article.
October 12, 2018: British Journal of Pharmacology
Yunxia Wang, Cong Chen, Qinyu Wang, Yini Cao, Lu Xu, Rong Qi
BACKGROUND AND PURPOSE: Abdominal aortic aneurysm (AAA) is a degenerative disease affecting human health. But there are no safe and effective medications for AAA therapy. Cycloastragenol (CAG), derived from Astragali Radix, has various pharmacological effects. But whether CAG can protect against AAA remains elusive. This study aims to investigate whether CAG has inhibitory effect on AAA and it's related mechanism. EXPERIMENTAL APPROACH: AAA mouse model was induced by incubating abdominal aorta of mice with elastase...
October 10, 2018: British Journal of Pharmacology
Li Jiang, Rong Dong, Meidan Ying, Qiaojun He, Ji Cao, Bo Yang
Retinoids, vitamin A and its natural and synthetic analogues have various functions, such as involvement in cell proliferation and differentiation and participation in the formation of the vertebrate morphology. In addition, they may activate certain tumour suppressor genes to perform functions in tumour inhibition. In the past decades, retinoids have been regarded as promising chemotherapeutic or chemopreventive agents; however, their mechanisms are still not fully understood. Immune cells that participate in or are related to the immune response play vital roles in the initiation and development of many cancers...
October 9, 2018: British Journal of Pharmacology
Gábor Pozsgai, István Zoárd Bátai, Erika Pintér
Hydrogen sulfide (H2 S) is a gaseous mediator in various physiological and pathological processes, including neuro-immune-modulation, metabolic pathways, cardiovascular system, tumour growth, inflammation and pain etc. Nowadays hydrogen polysulfides (H2 Sn ) have turned up as signalling molecules modulating ion channels, transcription factors and protein kinases. Transient Receptor Potential (TRP) cation channels can be activated by mechanical, thermal or chemical triggers. Here, we review the current literature regarding biological actions of sulfide and polysulfide compounds mediated by TRP-s with special emphasis on the role of TRPA1...
October 6, 2018: British Journal of Pharmacology
Valentina Giorgio, Federico Fogolari, Giovanna Lippe, Paolo Bernardi
The permeability transition pore (PTP) is a latent, high-conductance channel of the inner mitochondrial membrane. When activated, it plays a key role in cell death and therefore in several diseases. The pursuit of the PTP has taken an unexpected turn after the discovery that cyclophilin D (the target of the PTP inhibitory effect of cyclosporin A) binds FO F1 (F)-ATP synthase resulting in inhibition of its catalytic activity by about 30% [Giorgio et al. (2009) J. Biol. Chem. 284, 33982-33988]. This observation was followed by the demonstration that binding occurs at the oligomycin sensitivity conferral protein (OSCP) and that F-ATP synthase can form Ca2+ -activated, high conductance channels with features matching those of the PTP, suggesting that the latter originates from a conformational change of F-ATP synthase [Giorgio et al...
October 6, 2018: British Journal of Pharmacology
Binglan Yu, Fumito Ichinose, Donald B Bloch, Warren M Zapol
Nitric oxide (NO) is a gas that induces relaxation of smooth muscle cells in the vasculature. Because NO reacts with oxyhemoglobin with high affinity, the gas is rapidly scavenged by oxyhemoglobin in red blood cells and the vasodilating effects of inhaled NO are limited to ventilated regions in the lung. NO therefore has the unique ability to induce pulmonary vasodilation specifically in the portions of the lung with adequate ventilation, thereby improving oxygenation of blood and decreasing intrapulmonary right to left shunting...
October 4, 2018: British Journal of Pharmacology
Lisa M Broad, Helen E Sanger, Adrian J Mogg, Ellen M Colvin, Ruud Zwart, David A Evans, Francesca Pasqui, Emanuele Sher, Graham N Wishart, Vanessa N Barth, Christian C Felder, Paul J Goldsmith
BACKGROUND AND PURPOSE: The goal of this work was to identify and develop novel, selective muscarinic M1 receptor agonists as potential therapeutics for the symptomatic treatment of Alzheimer's disease. EXPERIMENTAL APPROACH: We developed and utilized a novel M1 receptor occupancy assay to drive a structure activity relationship in a relevant brain region, whilst simultaneously tracking drug levels in plasma and brain to optimize for central penetration. Functional activity was tracked in relevant native in vitro assays allowing translational (rat-human) benchmarking of SAR molecules to clinical comparators...
October 1, 2018: British Journal of Pharmacology
M F Bird, R Guerrini, J M Willets, J P Thompson, G Caló, D G Lambert
BACKGROUND AND PURPOSE: The nociception/orphanin FQ (N/OFQ) receptor (NOP) is a member of the opioid receptor family and is involved in a number of physiological responses; pain and immune regulation as examples. In this study we have conjugated a red flurophore-ATTO594 to the peptide ligand N/OFQ (N/OFQATTO594 ) for the NOP receptor and explored NOP function at high (in recombinant systems) and low (on immune cells) expression. EXPERIMENTAL APPROACH: We have assessed N/OFQATTO594 receptor binding, selectivity and functional activity in recombinant (CHO) cell lines...
October 1, 2018: British Journal of Pharmacology
Khaled Elmasry, Ahmed S Ibrahim, Samer Abdulmoneim, Mohamed Al-Shabrawey
Angiogenesis, disruption of the retinal barrier, leukocyte-adhesion, and oedema are cardinal signs of proliferative retinopathies that are associated with vision loss. Therefore, identifying factors that regulate these vascular dysfunctions is critical to target pathological angiogenesis. Given the conflicting role of bioactive lipids reported in the current literature, the goal of this review is to provide the reader a clear road map of what has been accomplished so far in the field with specific focus on the role of polyunsaturated fatty acids (PUFAs)-derived metabolites in proliferative retinopathies...
October 1, 2018: British Journal of Pharmacology
Zeng-Yan Huang, Ling-Jun Wang, Jia-Jia Wang, Wen-Jun Feng, Zhong-Qi Yang, Shi-Hao Ni, Yu-Sheng Huang, Huan Li, Yi Yang, Ming-Qing Wang, Rong Hu, Heng Wan, Chan-Juan Wen, Shao-Xiang Xian, Lu Lu
BACKGROUND AND PURPOSE: Liquorice is the root of Glycyrrhiza glabra, which is a popular food in Europe and China that has previously shown benefits for skeletal fatigue and nutrient metabolism. However, the mechanism and active ingredients remain largely unclear. The aim of this study was to investigate the active ingredients of liquorice for muscle wasting and elucidate the underlying mechanisms. EXPERIMENTAL APPROACH: RNA-Seq and bioinformatics analysis were applied to predict the main target of liquorice...
September 30, 2018: British Journal of Pharmacology
Dong-Jie Li, Jie Tong, Fei-Yan Zeng, Mengqi Guo, Yong-Hua Li, Hongbo Wang, Pei Wang
BACKGROUND AND PURPOSE: Platelet-derived growth factor-BB (PDGF-BB) is an angiogenic factor involved in cardiovascular diseases. Here, we investigated the possible effects of activation of nicotinic acetylcholine receptor α7 subtype (α7nAChR) on PDGF-BB-induced proliferation and migration in vascular smooth muscle cells (VSMCs). EXPERIMENTAL APPROACH: PNU-282987, a selective α7nAChR pharmacological agonist, was used to activate α7nAChR. The influences of α7nAChR activation on PDGF-BB-induced proliferation and migration, as well as the phosphorylation of focal adhesion kinase/Src, a pro-migration signaling pathway, were determined in VSMCs...
September 30, 2018: British Journal of Pharmacology
Alva Rosendahl, Reza Kabiri, Marlies Bode, Anna Cai, Stefanie Klinge, Heimo Ehmke, Hans-Willi Mittrücker, Ulrich O Wenzel
BACKGROUND AND PURPOSE: The adaptive immune response and contribute to renal damage in several experimental models of renal injury. EXPERIMENTAL APPROACH: To evaluate the role of the adaptive immune response 5/6 nephrectomy was performed in RAG-1 deficient mice that lack B and T cells. To further pin down the role of IL-17A we additionally performed 5/6 nephrectomy in IL-17A deficient mice...
September 30, 2018: British Journal of Pharmacology
Tianhui Liu, Ping Wang, Min Cong, Xinyan Zhao, Dong Zhang, Hufeng Xu, Lin Liu, Jidong Jia, Hong You
BACKGROUND AND PURPOSE: Diethyldithiocarbamate (DDC) is a major metabolite of disulfiram that is a potential drug for alcoholism treatment. In present study, we attempted to explore the possible effect of DDC on non-alcoholic fatty liver disease (NAFLD) and related fibrosis in vivo. EXPERIMENTAL APPROACH: C57BL/6 mice and SD rats received methionine/choline deficient (MCD) diet to establish the model of NAFLD with or without DDC treatment. The livers and serum were assessed for histological changes and parameters related to lipid metabolism, liver injury, inflammation and fibrosis...
September 28, 2018: British Journal of Pharmacology
Monika A Jakubowska, Martijn Kerkhofs, Claudio Martines, Dimitar G Efremov, Julia V Gerasimenko, Oleg V Gerasimenko, Ole H Petersen, Geert Bultynck, Tim Vervliet, Pawel E Ferdek
BACKGROUND AND PURPOSE: Many cancer cells depend on anti-apoptotic B cell lymphoma 2 (Bcl-2) proteins for their survival. Bcl-2 antagonism through BH3 mimetics emerged as novel anti-cancer therapy. ABT-199 (Venetoclax), a recently developed BH3 mimetic inhibiting selectively Bcl-2, was introduced into the clinic for treatment of relapsed chronic lymphocytic leukaemia. Early generations of Bcl-2 inhibitors evoked sustained Ca2+ responses in pancreatic acinar cells (PACs) inducing cell death...
September 28, 2018: British Journal of Pharmacology
M Antón, A Rodríguez-González, A Ballesta, N González, A Del Pozo, F R de Fonseca, M L Gómez-Lus, J C Leza, B García-Bueno, J R Caso, L Orio
BACKGROUND & PURPOSE: Chronic alcohol consumption alters the gut-brain axis, but little is known about alcohol binge episodes on the functioning of the intestinal barrier. We investigated the influence of ethanol binges on bacterial translocation, gut inflammation and immunity, and tight junction (TJ) structure, and the pharmacological effects of the biolipid oleoylethanolamide (OEA) in preventing ethanol binge-induced intestinal barrier dysfunction. EXPERIMENTAL APPROACH: OEA was administered intraperitoneally before repeated ethanol oral gavages, and plasma, spleen, liver and mesenteric lymph nodes (MLN) were collected in sterile conditions for determination of bacterial load...
September 24, 2018: British Journal of Pharmacology
Hussam M Daghistani, Bodour S Rajab, Ashraf Kitmitto
A hallmark of heart failure is mitochondrial dysfunction leading to a bioenergetics imbalance in the myocardium. Consequently, there is much interest in targeting mitochondrial abnormalities to attenuate the pathogenesis of heart failure. This review discusses i) how electron microscopy (EM) techniques have been fundamental for current understanding of mitochondrial structure-function ii) the paradigm shift in resolutions now achievable by 3-D EM techniques due to the introduction of direct detection devices and phase plate technology, and iii) the application of EM for unravelling mitochondrial pathological remodelling in heart failure...
September 18, 2018: British Journal of Pharmacology
Colin G Miller, Edward E Schmidt
Intermediary metabolism and detoxification place high demands on the disulfide reductase systems in most hepatocyte subcellular compartments. Biosynthetic, metabolic, cytoprotective, and signaling activities in the cytosol; regulation of transcription in nuclei; respiration in mitochondria; and protein folding in endoplasmic reticulum all require resident disulfide reductase activities. In the cytosol, two NADPH-dependent enzymes, glutathione reductase and thioredoxin reductase, as well as a recently identified NADPH-independent system that uses catabolism of methionine to maintain pools of reduced glutathione, supply disulfide reducing power...
September 17, 2018: British Journal of Pharmacology
Baris Alten, Metin Yesiltepe, Erva Bayraktar, Sadik Taskin Tas, Ayse Yesim Gocmen, Canan Kursungoz, Ana Martinez, Yildirim Sara
BACKGROUND AND PURPOSE: Children and adolescents are the top consumers of high fructose corn syrup (HFCS) sweetened beverages. Even though the cardiometabolic consequences of HFCS consumption in adolescents are well known, the neuropsychiatric consequences have yet to be determined. EXPERIMENTAL APPROACH: Adolescent rats were fed for a month with 11% weight/volume carbohydrate containing HFCS solution, which is similar to the sugar sweetened beverages of human consumption...
September 17, 2018: British Journal of Pharmacology
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