24,073 results match your criteria British journal of pharmacology[Journal]


Hydrogen sulfide abrogates heart valve calcification: Implications for calcific aortic valve disease.

Br J Pharmacol 2019 Apr 24. Epub 2019 Apr 24.

HAS-UD Vascular Biology and Myocardial Pathophysiology Research Group, Hungarian Academy of Sciences, Debrecen, Hungary.

Background And Purpose: Calcification of heart valves is a frequent pathological finding in CKD patients and in elderly. Hydrogen sulfide (H S) has been suggested to possess various anti-calcific actions. We aimed to investigate H S as a potential therapeutic in valvular calcification and to identify its targets in the pathogenesis. Read More

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http://dx.doi.org/10.1111/bph.14691DOI Listing

A cholecystokinin receptor agonist (CCK-8) induces adiponectin production in rat white adipose tissue.

Br J Pharmacol 2019 Apr 23. Epub 2019 Apr 23.

Departamento de Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia, Universidad CEU-San Pablo, Madrid, Spain.

Background And Purpose: A cholecystokinin (CCK) system has been identified in white adipose tissue (WAT). Nevertheless, the endocrine actions of CCK on WAT remain unknown. Our goal was to investigate the role of CCK in regulating the production of adiponectin, an adipokine expressed in WAT, which is pivotal in preserving energy homeostasis. Read More

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http://dx.doi.org/10.1111/bph.14690DOI Listing

Quantitative assessment of oligomeric amyloid beta peptide binding to alpha7 nicotinic receptor.

Br J Pharmacol 2019 Apr 13. Epub 2019 Apr 13.

Inserm U1016, Institut Cochin, Paris, 75014, France.

Background And Purpose: Progressive dysfunction of cholinergic transmission is a well-known characteristic of Alzheimer's Disease (AD). Amyloid beta (Aβ) peptide oligomers are known to play a central role in AD and are suggested to impair the function of the nicotinic acetylcholine receptor alpha 7 (α7nAChR). However, the mechanism underlying the effect of Aβ on α7nAChR function is not fully understood, limiting the therapeutic exploration of this observation in AD. Read More

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http://dx.doi.org/10.1111/bph.14688DOI Listing
April 2019
1 Read

A photoswitchable GABA receptor channel blocker.

Br J Pharmacol 2019 Apr 13. Epub 2019 Apr 13.

Aix-Marseille University, INSERM, INS, Institut de Neurosciences des Systèmes, 13005, Marseille, France.

Background And Purpose: Anion-selective Cys-loop receptors (GABARs and GlyRs) provide main inhibitory drive in CNS. Both types of receptors are operating via chloride-selective ion channels, however with different kinetics, pharmacological profiles and localization. Disequilibrium in their function leads to a variety of disorders, which are often treated with allosteric modulators. Read More

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http://dx.doi.org/10.1111/bph.14689DOI Listing

Blockage of myeloid differentiation 2 attenuates diabetic nephropathy via reducing local RAS activation in mouse kidneys.

Br J Pharmacol 2019 Apr 8. Epub 2019 Apr 8.

Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.

Background And Purpose: Both innate immunity and renin-angiotensin system (RAS) play important roles in the pathogenesis of diabetic nephropathy (DN). Myeloid differentiation factor 2 (MD2) is a co-receptor of toll-like receptor 4 (TLR4) in innate immunity. While TLR4 has been reported to mediate the development of DN, the role of MD2 in DN has not been characterized, and it also remains unclear whether MD2/TLR4 signaling pathway is associated with RAS activation in diabetes. Read More

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http://dx.doi.org/10.1111/bph.14687DOI Listing
April 2019
2 Reads

Inhibition of TLR4-mediated STAT3 activation attenuates Angiotensin II-induced renal fibrosis and dysfunction.

Br J Pharmacol 2019 Apr 8. Epub 2019 Apr 8.

Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.

Background And Purpose: Hypertension adversely affects the kidney and is the second leading cause of kidney failure. Overproduction of angiotensin II (Ang II) greatly contributes to the progression of hypertensive kidney disease. Ang II has recently been shown to activate signal transducer and activator of transcription 3 (STAT3) in cardiovascular cells. Read More

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http://dx.doi.org/10.1111/bph.14686DOI Listing
April 2019
1 Read

Expression of Concern: Kumar P, Kalonia H and Kumar A. 2011, Role of LOX/COX pathways in 3-nitropropionic acid-induced Huntington's disease-like symptoms in rats: Protective effect of licofelone. Brit J Pharmacol 164: 644-654. doi: 10.1111/j.1476-5381.2011.01418.x.

Authors:

Br J Pharmacol 2019 04 28;176(8):1170. Epub 2019 Mar 28.

This expression of concern is for the above article, published online on April 12, 2011, in Wiley Online Library (wileyonlinelibrary.com), and has been published by agreement between the journal Editor-in-Chief, the British Pharmacological Society, and John Wiley & Sons, Ltd. The expression of concern has been agreed due to concerns regarding data presented within the article. Read More

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http://dx.doi.org/10.1111/bph.14655DOI Listing

Oiling the wheels of discovery.

Br J Pharmacol 2019 Apr;176(8):985-987

The William Harvey Research Institute, Queen Mary University of London, London, UK.

Linked Articles: This article is part of a themed section on Eicosanoids 35 years from the 1982 Nobel: where are we now? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10. Read More

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http://dx.doi.org/10.1111/bph.14588DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6451071PMC

Sex as a biological variable in the pathology and pharmacology of neurodegenerative and neurovascular diseases.

Br J Pharmacol 2019 Apr 4. Epub 2019 Apr 4.

University of Texas McGovern Medical School, Department of Neurology, Fannin Street, Houston, TX, 77030.

The incidence of dementia, most commonly caused by cerebrovascular and neurodegenerative diseases, continues to grow as our population ages. Alzheimer disease (AD) and vascular cognitive impairment (VCI) are responsible for more than 80% of all cases of dementia. There are few effective, long-term treatments for AD and VCI-related conditions (e. Read More

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http://dx.doi.org/10.1111/bph.14675DOI Listing
April 2019
1 Read

Model-free and kinetic modelling approaches for characterising non-equilibrium pharmacological pathway activity: CB cannabinoid receptor internalisation.

Br J Pharmacol 2019 Apr 3. Epub 2019 Apr 3.

Otago Pharmacometrics Group, School of Pharmacy, University of Otago, Dunedin, New Zealand.

Background And Purpose: Receptor internalisation is by nature kinetic. Application of a standard equilibrium dose response model to describe the properties of a ligand inducing internalisation, while commonly used, are therefore problematic. Here, we propose two quantitative approaches to address this issue - (1) a model-free method and (2) a kinetic modelling approach - and systematically evaluate the performance of these methods against traditional equilibrium methods to characterise the internalisation profiles of cannabinoid CB1 agonists. Read More

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http://dx.doi.org/10.1111/bph.14684DOI Listing

Bradykinin increases blood pressure in endotoxemic rats: functional and biochemical evidence of angiotensin II type 1/bradykinin B2 receptor heterodimerization.

Br J Pharmacol 2019 Apr 3. Epub 2019 Apr 3.

Departament of Pharmacology, Laboratory of Cardiovascular Biology, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, Brazil.

Background And Purpose: It has been shown that bradykinin may induce vasoconstriction in selected vessels or under specific experimental conditions. We hypothesized that inflammatory stimuli, such as endotoxin challenge, may induce the dimerization of AT1/B2 receptors, altering the vascular effects of bradykinin.

Experimental Approach: Wistar rats received LPS (1 mg kg , i. Read More

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http://dx.doi.org/10.1111/bph.14685DOI Listing

Sulindac-derived RXRα modulator attenuates atherosclerotic plaque progression and destabilization in ApoE mice.

Br J Pharmacol 2019 Apr 3. Epub 2019 Apr 3.

From the Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Background And Purpose: Atherosclerosis is a chronic inflammatory disease, and retinoid X receptor alpha (RXRα) is an intriguing anti-atherosclerosis target. This study investigated whether and how an RXRα modulator, K-80003, derived from a non-steroidal anti-inflammatory drug (NSAID) attenuates atherosclerotic plaque progression and destabilization.

Experimental Approach: Our previously established ApoE mouse model of carotid vulnerable plaque progression was treated with K-80003 or vehicle for 4 or 8 weeks. Read More

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http://dx.doi.org/10.1111/bph.14682DOI Listing

(R)-ketamine exerts antidepressant actions partly via conversion to (2R,6R)-hydroxynorketamine, while causing adverse effects at sub-anesthetic doses.

Br J Pharmacol 2019 Apr 2. Epub 2019 Apr 2.

Department of Psychiatry, University of Maryland, Baltimore, School of Medicine, Baltimore, Maryland, United States.

Background And Purpose: (R)-ketamine (arketamine) may have utility as a rapid-acting antidepressant. While (R)-ketamine has lower potency than (R,S)-ketamine to inhibit the N-methyl-D-aspartate receptor (NMDAR) in vitro, the extent to which (R)-ketamine shares the NMDAR-mediated adverse effects of (R,S)-ketamine in vivo has not been fully characterised. Furthermore, (R)-ketamine is metabolised to (2R,6R)-hydroxynorketamine (HNK), which may contribute to its antidepressant-relevant actions. Read More

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http://dx.doi.org/10.1111/bph.14683DOI Listing
April 2019
3 Reads

β-Adrenoceptor stimulation upregulates cardiac expression of galectin-3 and BIM through the Hippo signalling pathway.

Br J Pharmacol 2019 Apr 1. Epub 2019 Apr 1.

Experimental Cardiology Laboratory, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia.

Background And Purpose: Expression of the pro-fibrotic galectin-3 and the pro-apoptotic BIM is elevated in diseased heart or β-adrenoceptor (βAR) stimulation, but the responsible mechanism is unclear. This question was addressed in the present study.

Experimental Approach: Wild-type mice and mice with cardiac transgenic expression of β AR, mammalian sterile-20 like kinase1 (Mst1) or dominant-negative Mst1, and non-specific galectin-3 knockout mice were used. Read More

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http://dx.doi.org/10.1111/bph.14674DOI Listing
April 2019
1 Read

Inactivation of endothelial adenosine receptor 2A protects mice from cerebral ischemia-induced brain injury.

Br J Pharmacol 2019 Mar 31. Epub 2019 Mar 31.

Vascular Biology Center, Medical College of Georgia, Augusta University, Augusta, GA, 30912, USA.

Background And Purpose: Adenosine receptor 2A (ADORA2A for humans, Adora2a for rodents) inactivation protects against brain injury in experimental stroke; however, the cell-specific pathogenic effects of Adora2a in thromboembolic (TE)-stroke and the underlying mechanisms remain understudied. Here, we tested the hypothesis that inhibition of endothelial Adora2a after TE-stroke improves post-stroke outcomes via downregulation of inflammation.

Experimental Approach: TE-stroke was induced via embolic middle cerebral artery occlusion (eMCAo) in mice. Read More

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http://dx.doi.org/10.1111/bph.14673DOI Listing
March 2019
2 Reads

Short lipopeptides specifically inhibit the growth of Propionibacterium acnes with antibacterial and anti-inflammatory dual action.

Br J Pharmacol 2019 Mar 30. Epub 2019 Mar 30.

Group of peptides and natural products Research, School of Pharmaceutical Sciences, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou, 510515, P.R. China.

Background And Purpose: Propionibacterium acnes (P. acnes) is a Gram-positive bacterium associated with the skin disorder acne. In this study, considering the importance of fatty acids in the life habitat of P. Read More

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http://dx.doi.org/10.1111/bph.14680DOI Listing
March 2019
1 Read

Amlodipine induces vasodilation via Akt2/Sp1-activated miR-21 in smooth muscle cells.

Br J Pharmacol 2019 Mar 30. Epub 2019 Mar 30.

Division of Cardiology, Departments of Internal Medicine and Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

Objective: The calcium antagonist amlodipine exerts important cardioprotective effects by modulating smooth muscle and endothelial functions. However, the mechanisms underlying these effects are incompletely understood.

Approach And Results: Only the calcium antagonist amlodipine, and no other type of anti-hypertensive drugs, induced miR-21 overexpression in plasma and aortic vessels in the animal model. Read More

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http://dx.doi.org/10.1111/bph.14679DOI Listing
March 2019
3 Reads
4.842 Impact Factor

Oral administration of a new HRI activator as a new strategy to improve High-Fat-Diet-induced glucose intolerance, hepatic steatosis and hypertriglyceridemia through FGF21.

Br J Pharmacol 2019 Mar 30. Epub 2019 Mar 30.

Department of Pharmacology, Toxicology and Therapeutic Chemistry, Faculty of Pharmacy, University of Barcelona, Institute of Biomedicine of the University of Barcelona (IBUB), Barcelona, Spain.

Background And Purpose: Fibroblast growth factor 21 (FGF21) has emerged as a therapeutic strategy for treating type 2 diabetes mellitus due to its antidiabetic effects, and this has led to the development of FGF21 long-acting analogs. These compounds have some limitations, including requiring subcutaneous injection and their prolonged pharmacodynamic effect compared with native FGF21, which might be responsible for their reported side effects.

Experimental Approach: We have previously demonstrated that intraperitoneal administration of heme-regulated eukaryotic translation initiation factor 2α (eIF2α) kinase (HRI) activators increases hepatic and circulating levels of FGF21. Read More

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http://dx.doi.org/10.1111/bph.14678DOI Listing
March 2019
1 Read

Action of MK-7264 (Gefapixant) at human P2X3 and P2X2/3 receptors and in vivo efficacy in models of sensitisation.

Br J Pharmacol 2019 Mar 30. Epub 2019 Mar 30.

Biomedical Research Centre, School of Biological Sciences, University of East Anglia, Norwich Research Park, NR4 7TJ.

Background & Purpose: The P2X3 receptor is an ATP-gated ion channel expressed by sensory afferent neurons, and is as a target to treat chronic sensitisation conditions. The first-in-class, selective P2X3 and P2X2/3 receptor antagonist, the diaminopyrimidine MK-7264 (Gefapixant), has progressed to Phase III trials for refractory or unexplained chronic cough. We have used patch-clamp to elucidate the pharmacology and kinetics of MK-7264 and rat models of hypersensitivity and hyperalgesia to test efficacy in these conditions. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1111/bph.14677
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http://dx.doi.org/10.1111/bph.14677DOI Listing
March 2019
7 Reads

Analgesic TRPV1-active compounds inhibit native and recombinant T-type (Ca 3) calcium channels.

Br J Pharmacol 2019 Mar 30. Epub 2019 Mar 30.

Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, NSW, 2522, Australia.

Background And Purpose: T-type calcium (Ca 3) and transient receptor potential vanilloid-1 (TRPV1) channels play central roles in the control of excitability in the peripheral nervous system and are regarded as potential therapeutic pain targets. Modulators that either activate or inhibit TRPV1-mediated currents display analgesic properties in various pain models despite opposing effects on their connate target, TRPV1. We explore the effects of TRPV1-active compounds on Ca 3-mediated currents. Read More

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http://dx.doi.org/10.1111/bph.14676DOI Listing

Chemistry, pharmacology and cellular uptake mechanisms of thiometallate sulfide donors.

Br J Pharmacol 2019 Mar 29. Epub 2019 Mar 29.

Bloomsbury Institute of Intensive Care Medicine, Division of Medicine, University College London, Gower St, London, WC1E 6BT, UK.

Background And Purpose: A clinical need exists for targeted, safe and effective sulfide donors. We recently reported that ammonium tetrathiomolybdate (ATTM) belongs to a new class of sulfide-releasing drugs. Here, we investigate cellular uptake mechanisms of this drug class compared to sodium hydrosulfide (NaHS), and report on the thiometallate tungsten congener of ATTM, ammonium tetrathiotungstate (ATTT). Read More

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http://dx.doi.org/10.1111/bph.14670DOI Listing
March 2019
3 Reads

Influence of sildenafil on the purinergic components of nerve-mediated and urothelial ATP release from the bladder of normal and spinal cord injured mice.

Br J Pharmacol 2019 Mar 29. Epub 2019 Mar 29.

School of Physiology, Pharmacology, and Neuroscience, University of Bristol, Bristol, UK.

Background And Purpose: PDE inhibitors such as sildenafil alleviate lower urinary tract symptoms, however a complete understanding of their action on the bladder remains unclear. We are investigating the effects of sildenafil, on post- and pre-ganglionic nerve-mediated contractions of the mouse bladder, and neuronal and urothelial ATP release.

Experimental Approach: Bladders were used from young (12 weeks), aged (24 months), and spinal cord transected (SCT), mice, for in vitro contractility experiments. Read More

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http://dx.doi.org/10.1111/bph.14669DOI Listing

The Potential of Memory Enhancement through Perineuronal Net Modulation.

Br J Pharmacol 2019 Mar 29. Epub 2019 Mar 29.

School of Biomedical Sciences, University of Leeds, Leeds, LS2 9JT, UK.

With an increasingly aging global population, the incidence of neurological diseases such as dementia are set to increase to unmanageable levels, yet there are currently only symptomatic therapies available for treatment. The mechanisms underlying the development of some forms of dementia, such as Alzheimer's disease (AD), are not yet completely elucidated with several competing hypotheses existing. During the closure of the critical period in the brain, significant compositional changes occur to the neural extracellular matrix (ECM). Read More

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http://dx.doi.org/10.1111/bph.14672DOI Listing
March 2019
1 Read

VU0810464, a non-urea GIRK channel activator, exhibits enhanced selectivity for neuronal GIRK channels and reduces stress-induced hyperthermia in mice.

Br J Pharmacol 2019 Mar 29. Epub 2019 Mar 29.

Department of Pharmacology, University of Minnesota, Minneapolis, MN.

Background And Purpose: G protein-gated inwardly rectifying K (GIRK) channels moderate the activity of excitable cells and have been implicated in neurological disorders and cardiac arrhythmias. Most neuronal GIRK channels contain GIRK1 and GIRK2 subunits (GIRK1/2 channels), while cardiac GIRK channels contain GIRK1 and GIRK4 (GIRK1/4 channels). Previously, we identified a family of urea-containing GIRK channel activators, but these molecules exhibit sub-optimal pharmacokinetic properties and modest selectivity for GIRK1/2 relative to GIRK1/4 channels. Read More

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http://dx.doi.org/10.1111/bph.14671DOI Listing
March 2019
1 Read

Therapeutic Targeting of Nuclear Receptors, LXR and RXR, for Alzheimer's Disease.

Br J Pharmacol 2019 Mar 29. Epub 2019 Mar 29.

Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, PA, 15261.

After 15 years of research into Alzheimer's disease (AD) therapeutics, including billions of US dollars provided by federal agencies, pharmaceutical companies and private foundations, there are still no meaningful therapies that can delay the onset or slow the progression of AD. Understanding of the proteolytic processing of Amyloid Precursor Protein (APP) and the hypothesis that pathogenic mechanisms in familial and sporadic forms of AD are very similar, led to the assumption that pharmacological inhibition of secretases or immunological approaches to clear amyloid depositions in brain would have been the core of drug discovery strategies and successful therapies. However, there are other understudied approaches including: targeting genes, gene networks and metabolic pathways outside the proteolytic processing of APP. Read More

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http://dx.doi.org/10.1111/bph.14668DOI Listing

Recent developments in research of melatonin and its potential therapeutic applications.

Authors:
S C Stanford

Br J Pharmacol 2018 Aug;175(16):3187-3189

Department of Neuroscience, Physiology and Pharmacology, University College London, London, UK.

Linked Articles: This article is part of a themed section on Recent Developments in Research of Melatonin and its Potential Therapeutic Applications. To view the other articles in this section visit http://onlinelibrary.wiley. Read More

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http://dx.doi.org/10.1111/bph.14371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6057894PMC

Correction.

Authors:

Br J Pharmacol 2019 Apr 27;176(7):981. Epub 2019 Feb 27.

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http://dx.doi.org/10.1111/bph.14629DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6433642PMC

Optostimulation of striatonigral terminals in substantia nigra induces dyskinesia that increases after L-DOPA in a mouse model of Parkinson's disease.

Br J Pharmacol 2019 Mar 21. Epub 2019 Mar 21.

Instituto Cajal, Consejo Superior de Investigaciones Científicas, CSIC, Avda Dr Arce 37, 28002, Madrid, Spain.

Background And Purpose: L-DOPA-induced dyskinesia (LID) remains a major complication of L-DOPA therapy in Parkinson's disease. LID is believed to result from inhibition of substantia nigra reticulata (SNr) neurons by GABAergic striatal projection neurons that become supersensitive to dopamine receptor stimulation after severe nigrostriatal degeneration. Here we asked if stimulation of direct medium spiny neuron (dMSN) GABAergic terminals at the SNr can produce a full dyskinetic state similar to that induced by L-DOPA. Read More

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http://dx.doi.org/10.1111/bph.14663DOI Listing
March 2019
4 Reads

Retinal and circulating miRNA expression patterns in diabetic retinopathy: an in silico and in vivo approach.

Br J Pharmacol 2019 Mar 18. Epub 2019 Mar 18.

Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, Catania, Italy.

Background And Purpose: Diabetic retinopathy, a secondary complication of diabetes mellitus, can lead to irreversible vision loss. Currently, no treatment is approved for early phases of diabetic retinopathy. Modifications of the expression pattern of miRNAs could be involved in the early retinal damage of diabetic subjects. Read More

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http://dx.doi.org/10.1111/bph.14665DOI Listing
March 2019
1 Read

"Activation of Kv7 channels as a novel mechanism for NO/cGMP-induced pulmonary vasodilation".

Br J Pharmacol 2019 Mar 18. Epub 2019 Mar 18.

Department of Pharmacology and Toxicology, School of Medicine, University Complutense of Madrid, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid.

Background And Purpose: The nitric oxide-NO/cGMP pathway represents a major physiological signalling controlling pulmonary arterial (PA) tone and drugs activating this pathway are used to treat pulmonary arterial hypertension. Kv channels expressed in PA smooth muscle cells (PASMC) are key determinants of vascular tone. We aimed to analyse the contribution of Kv1. Read More

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http://dx.doi.org/10.1111/bph.14662DOI Listing
March 2019
3 Reads

Serelaxin enhances the therapeutic effects of human amnion epithelial cell-derived exosomes in experimental models of lung disease.

Br J Pharmacol 2019 Mar 18. Epub 2019 Mar 18.

Cardiovascular Disease Program, Monash Biomedicine Discovery Institute and Department of Pharmacology, Monash University, Clayton, Victoria, Australia.

Background And Purpose: There has been growing interest in stem cell-derived exosomes for their therapeutic and regenerative benefits given their manufacturing and regulatory advantages over cell-based therapies. As existing fibrosis can significantly impede the viability and efficacy of stem cell/exosome-based strategies for treating chronic diseases, we determined if the anti-fibrotic drug, serelaxin, would further benefit the therapeutic efficacy of human amnion epithelial cell (AEC)-derived exosomes in experimental lung disease.

Experimental Approach: Female Balb/c mice were subjected to either the 9. Read More

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http://dx.doi.org/10.1111/bph.14666DOI Listing

Phosphodiesterase-4 inhibition attenuates murine ulcerative colitis via interfering with mucosal immunity.

Br J Pharmacol 2019 Mar 18. Epub 2019 Mar 18.

Laboratory of Anti-inflammation, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.

Background And Purpose: Ulcerative colitis (UC) is an etiologically refractory inflammatory disease, accompanied by dysfunction of epithelial barrier and intestinal inflammation. PDE4 serves as an intracellular proinflammatory enzyme targeting for degradation of cAMP. Though PDE4 inhibitors have been approved for pulmonary and dermatological diseases, the role of PDE4 inhibition in modulating mucosal immunity remains elusive. Read More

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http://dx.doi.org/10.1111/bph.14667DOI Listing
March 2019
2 Reads

Impaired clearance of sunitinib leads to metabolic disorders and hepatotoxicity.

Br J Pharmacol 2019 Mar 15. Epub 2019 Mar 15.

State Key Laboratory of Phytochemistry and Plant Resources in West China Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China.

Background And Purpose: Sunitinib is a small molecule tyrosine kinase inhibitor associated with hepatotoxicity. The mechanisms of its toxicity are still unclear.

Experimental Approach: In the present study, mice were treated with 60 mg kg-1, 150 mg kg-1, and 450 mg kg-1 sunitinib to evaluate sunitinib hepatotoxicity. Read More

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http://dx.doi.org/10.1111/bph.14664DOI Listing
March 2019
4 Reads

Discovery of early life stress interacting and sex-specific quantitative trait loci impacting cocaine responsiveness.

Br J Pharmacol 2019 Mar 15. Epub 2019 Mar 15.

Department of Psychological & Brain Sciences, University of California Santa Barbara, Santa Barbara, CA, 93106.

Background And Purpose: Addiction vulnerability involves complex gene X environment interactions leading to a pathological response to drugs. Identification of the genes mediating these interactions is an important step in understanding the underlying neurobiology and rarely have such analyses examined sex-specific influences. To dissect this interaction, we examined the impact of prenatal stress (PNS) on cocaine responsiveness in male and female mice of the BXD recombinant inbred panel. Read More

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http://dx.doi.org/10.1111/bph.14661DOI Listing
March 2019
1 Read

β3-adrenoceptor as a potential immuno-suppressor agent in melanoma.

Br J Pharmacol 2019 Mar 15. Epub 2019 Mar 15.

Neonatal Intensive Care Unit, Medical Surgical Fetal-Neonatal Department, Meyer "University Children's Hospital, Florence, Italy.

Background And Purpose: Stress-related catecholamines have a role in cancer and β-adrenoceptors, specifically β2-adrenoceptors have been identified as new targets in treating melanoma. Recently, β3-adrenoceptors have shown a pleiotropic effect on melanoma microenvironment leading to cancer progression. However, the mechanisms by which β3-adrenoceptors promote this progression remain poorly understood. Read More

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http://dx.doi.org/10.1111/bph.14660DOI Listing
March 2019
2 Reads

β -Adrenoceptors in the normal and diseased urinary bladder - what are the open questions?

Br J Pharmacol 2019 Mar 14. Epub 2019 Mar 14.

Department of Pharmacology, Johannes Gutenberg University, Mainz, Germany.

β -Adrenoceptor (β -AR) agonists are used in the treatment of overactive bladder syndrome (OAB). Although the relaxant response to adrenergic stimulation in human detrusor smooth muscle cells is mediated mainly via β -AR s, the plasma concentrations of the therapeutic dose of mirabegron, the only clinically approved β -AR agonist, are considerably lower than the EC for causing direct relaxation of human detrusor, suggesting the mechanism of action other than direct relaxation of detrusor smooth muscle. However, the site and mechanism of action of β -AR agonists in the bladder have not been firmly established. Read More

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http://dx.doi.org/10.1111/bph.14658DOI Listing

Androgen receptor antagonism accelerates disease onset in the SOD1 mouse model of amyotrophic lateral sclerosis.

Br J Pharmacol 2019 Mar 8. Epub 2019 Mar 8.

Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, 3052, Australia.

Background And Purpose: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease typically more common in males, implicating androgens in progression of both patients and mouse models. Androgen effects are mediated by the androgen receptor (AR) which is highly expressed in spinal motor neurons and skeletal muscles. To clarify the role of AR in ALS, we therefore examined the effect of AR antagonism in the SOD1 mouse model. Read More

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http://dx.doi.org/10.1111/bph.14657DOI Listing
March 2019
2 Reads

PIAS1 Ser-503 phosphorylation-mediated Elk-1 SUMOylation promotes neuronal survival in APP/PS1 mice.

Br J Pharmacol 2019 Mar 8. Epub 2019 Mar 8.

Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.

Background And Purpose: PIAS1 is phosphorylated by IKKα at Ser-90 in a PIAS1 E3 ligase activity-dependent manner. Whether PIAS1 is also phosphorylated at other residues, and what potential functional significance such additional phosphorylation events might have, are not known. The transcription factor Elk-1 remains SUMOylated under basal conditions, but the role of Elk-1 SUMOylation in the brain is unknown. Read More

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http://dx.doi.org/10.1111/bph.14656DOI Listing

L-cysteine/cystathionine-β-synthase-induced relaxation in mouse aorta involves a L-serine/sphingosine-1-phosphate/NO pathway.

Br J Pharmacol 2019 Mar 5. Epub 2019 Mar 5.

Department of Pharmacy, School of Medicine, University of Naples Federico II, Naples, Italy.

Background And Purpose: Among the three enzymes involved in the transsulfuration pathway, only cystathionine β-synthase (CBS) converts L-cysteine into L-serine and H S. L-serine is also involved in the de novo sphingolipid biosynthesis through a condensation with palmitoyl-CoA by the action of serine palmitoyltransferase (SPT). Here, we have investigated if L-serine contributes to the vasorelaxant effect. Read More

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http://dx.doi.org/10.1111/bph.14654DOI Listing

A proof-of-concept, Phase 2 clinical trial of the gastrointestinal safety of a hydrogen sulfide-releasing anti-inflammatory drug.

Br J Pharmacol 2019 Mar 4. Epub 2019 Mar 4.

National Institute of Oncology, Budapest, Hungary.

Background And Purpose: ATB-346 is a hydrogen sulfide (H S)-releasing anti-inflammatory and analgesic drug. Animal studies demonstrated negligible gastrointestinal (GI) damage despite marked inhibition of COX activity and significant analgesic and anti-inflammatory effects. In humans, ATB-346 (250 mg once daily) was found to inhibit COX to the same extent as naproxen (550 mg twice daily). Read More

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http://dx.doi.org/10.1111/bph.14641DOI Listing
March 2019
3 Reads

The specialised pro-resolving lipid mediator maresin 1 reduces inflammatory pain with a long-lasting analgesic effect.

Br J Pharmacol 2019 Mar 4. Epub 2019 Mar 4.

Department of Pathology, Centre of Biological Sciences, Londrina State University, Londrina, Brazil.

Background And Purpose: Maresin 1 (MaR1) is a specialised pro-resolving lipid mediator with anti-inflammatory and analgesic activities. In this study, we addressed the modulation of peripheral and spinal cord cells by MaR1 in the context of inflammatory pain.

Experimental Approach: Mice were treated with MaR1 before intraplantar injection of carrageenan or complete Freund's adjuvant (CFA). Read More

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http://dx.doi.org/10.1111/bph.14647DOI Listing
March 2019
1 Read
4.842 Impact Factor

Enhanced responsiveness of platelets to vicagrel in IL-10-deficient mice through STAT3-dependent up-regulation of the hydrolase arylacetamide deacetylase in the intestine.

Br J Pharmacol 2019 Mar 2. Epub 2019 Mar 2.

General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.

Background And Purpose: Vicagrel is a novel promising antiplatelet drug designed for overcoming clopidogrel resistance. There is limited evidence indicating that exogenous IL-10 suppresses CYP3A4 activity in healthy subjects and that IL-10 knockout (KO) mice exhibit increased clopidogrel bioactivation compared with wild-type (WT) mice. In this study, we sought to determine whether IL-10 could play an important role in the metabolism of and platelet response to vicagrel in mice. Read More

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http://dx.doi.org/10.1111/bph.14646DOI Listing

Erucin exhibits vasorelaxing effects and antihypertensive activity by H S-releasing properties.

Br J Pharmacol 2019 Mar 2. Epub 2019 Mar 2.

Department of Pharmacy, University of Pisa, Pisa, Italy.

Background And Purpose: Hydrogen sulfide (H S)-releasing agents are viewed as potential antihypertensive drugs. Recently, natural isothiocyanates emerged as original H S-donor agents. Among them, erucin, present in some edible cruciferous plants, shows suitable H S-releasing properties and features of "druggability. Read More

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http://dx.doi.org/10.1111/bph.14645DOI Listing

Identification of TAK-632 and its analogues as potent inhibitors of necroptosis by targeting RIPK1 and RIPK3.

Br J Pharmacol 2019 Mar 1. Epub 2019 Mar 1.

National Center for Liver Cancer, 366 Qianju Road, Shanghai, 201805, China.

Background And Purpose: Necroptosis is a form of programmed, caspase-independent cell death that is mediated by receptor-interacting protein kinases, RIPK1 and RIPK3, and the mixed lineage kinase domain-like (MLKL). Necroptosis contributes to the pathophysiology of various inflammatory, infectious and degenerative diseases. Thus, identification of small molecule inhibitors for necroptosis has broad therapeutic relevance. Read More

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http://dx.doi.org/10.1111/bph.14653DOI Listing
March 2019
1 Read

Hypoxia modulates protein phosphatase 2A through HIF-1α dependent and independent mechanisms in human aortic smooth muscle cells and ventricular cardiomyocytes.

Br J Pharmacol 2019 Mar 1. Epub 2019 Mar 1.

Department of Pharmacology and Therapeutics, Trinity College Dublin, Dublin, Ireland.

Background And Purpose: Although protein phosphatases regulate multiple cellular functions, their modulation under hypoxia remains unclear. We investigated expression of the protein phosphatase system under normoxic/hypoxic conditions and the mechanism by which hypoxia alters protein phosphatase 2A (PP2A) activity.

Experimental Approach: Human cardiovascular cells were cultured in cell type specific media under normoxic or hypoxic conditions (1% O ). Read More

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http://dx.doi.org/10.1111/bph.14648DOI Listing
March 2019
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Diosmetin induces apoptosis and enhances the chemotherapeutic efficacy of paclitaxel in non-small cell lung cancer cells via Nrf2 inhibition.

Br J Pharmacol 2019 Mar 1. Epub 2019 Mar 1.

Department of Clinical pharmacy, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, China.

Background And Purpose: Non-small cell lung cancer (NSCLC) accounts for up to 80-85% of all lung cancers with a disappointing prognosis. Flavonoids exert anti-cancer properties, mostly involving stimulation of ROS production without significant toxicity to normal cells. This study was aimed to delineate the effect of diosmetin, a natural flavonoid, on NSCLC cells and the ability to enhance the anti-tumour activity of paclitaxel. Read More

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http://dx.doi.org/10.1111/bph.14652DOI Listing
March 2019
4 Reads
4.842 Impact Factor

Cyclic nucleotide signalling compartmentation by phosphodiesterases in cultured vascular smooth muscle cells.

Br J Pharmacol 2019 Mar 1. Epub 2019 Mar 1.

UMR-S 1180, INSERM, Univ Paris-Sud, Université Paris-Saclay, Châtenay-Malabry, France.

Background And Purpose: PDE upregulation is associated with several vascular diseases and better understanding of the respective role of each PDE family in controlling subcellular pools of cyclic nucleotides in vascular cells is needed. We investigated the respective role of PDE1, PDE5 and PDE9 in controlling intracellular cAMP and/or cGMP concentrations ([cAMP] , [cGMP] ) in cultured rat aortic smooth muscle cells (RASMCs).

Experimental Approach: By using a pharmacological approach with selective PDE1, PDE5 and PDE9 inhibitors (PF-04471141, sildenafil and PF-04447943, respectively), cAMP- and cGMP-PDE activities were measured by a radioenzymatic assay in protein extracts. Read More

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http://dx.doi.org/10.1111/bph.14651DOI Listing
March 2019
26 Reads

Small molecule-facilitated anion transporters in cells for a novel therapeutic approach to cystic fibrosis.

Br J Pharmacol 2019 Mar 1. Epub 2019 Mar 1.

Istituto di Biofisica, CNR, Genova, Italy.

Background And Purpose: Cystic fibrosis (CF) is a lethal autosomal recessive genetic disease that originates from the defective function of the CF transmembrane conductance regulator (CFTR) protein, a cAMP-dependent anion channel involved in fluid transport across epithelium. Because small synthetic transmembrane anion transporters (anionophores) can replace the biological anion transport mechanisms, independent of genetic mutations in the CFTR, such anionophores are candidates as new potential treatments for CF.

Experimental Approach: In order to assess their effects on cell physiology, we have analysed the transport properties of five anionophore compounds, three prodigiosines and two tambjamines. Read More

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http://dx.doi.org/10.1111/bph.14649DOI Listing
March 2019
3 Reads

Simvastatin Protects Photoreceptors from all-trans-retinal Induced Oxidative Stress with Up-regulation of Interphotoreceptor Retinoid Binding Protein.

Br J Pharmacol 2019 Mar 1. Epub 2019 Mar 1.

Save Sight Institute, The University of Sydney, Sydney, NSW, Australia.

Background And Purpose: Simvastatin is a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor with multiple targets and effects. It protects neurons in the brain but its protective effects on photoreceptors are unclear. In this study, we evaluated the neuroprotective effect of simvastatin on photoreceptors exposed to stress induced by all-trans-retinal (atRAL). Read More

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http://dx.doi.org/10.1111/bph.14650DOI Listing
March 2019
2 Reads

S-NITROSOGLUTATHIONE INHIBITS CEREBROVASCULAR ANGIOTENSIN II DEPENDENT AND INDEPENDENT AT RECEPTOR RESPONSES: A POSSIBLE ROLE OF S-NITROSATION.

Br J Pharmacol 2019 Mar 1. Epub 2019 Mar 1.

Université de Lorraine, CITHEFOR, F-54000, Nancy, France.

Background And Purpose: Angiotensin II (AngII) and nitric oxide (NO) regulate cerebral circulation. AngII AT receptors exert ligand-dependent and -independent (myogenic tone, MT) vasoconstriction of cerebral vessels. NO induces post-translational modifications of proteins such as S-nitrosation (redox modification of cysteine residues). Read More

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http://dx.doi.org/10.1111/bph.14644DOI Listing
March 2019
2 Reads