24,528 results match your criteria British journal of pharmacology[Journal]


Tackling COVID-19 infection through complement-targeted immunotherapy.

Br J Pharmacol 2020 Jul 9. Epub 2020 Jul 9.

Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.

The complement system is an ancient part of innate immunity sensing highly pathogenic coronaviruses by mannan-binding lectin (MBL) resulting in lectin pathway activation and subsequent generation of the anaphylatoxins (AT) C3a and C5a as important effector molecules. Complement deposition on endothelial cells and high blood C5a serum levels have been reported in COVID-19 patients with severe illness, suggesting vigorous complement activation leading to systemic thrombotic microangiopathy (TMA). Complement regulator gene variants prevalent in African Americans have been associated with a higher risk for severe TMA and multi-organ injury. Read More

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http://dx.doi.org/10.1111/bph.15187DOI Listing

Proteinase-activated receptor 1 (PAR1): A target for repurposing in the treatment of COVID-19?

Br J Pharmacol 2020 Jul 8. Epub 2020 Jul 8.

Departments of Pharmacology and Medicine, University of California San Diego, La Jolla, California, 92093, USA.

In the search to rapidly identify effective therapies that will mitigate the morbidity and mortality of COVID-19, attention has been directed towards the repurposing of existing drugs. Candidates for repurposing include drugs that target COVID-19 pathobiology, including agents that alter angiotensin signaling. Recent data indicate that key findings in COVID-19 patients include thrombosis and endothelitis. Read More

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http://dx.doi.org/10.1111/bph.15194DOI Listing

Translational engagement of LPA receptor in skin fibrosis: from dermal fibroblasts of patients with scleroderma to Tsk1 mouse.

Br J Pharmacol 2020 Jul 5. Epub 2020 Jul 5.

Sanofi, Cardiovascular & Metabolism Unit, 1 avenue Pierre Brossolette, 91385, Chilly-Mazarin, France.

Background And Purpose: Genetic deletion and pharmacological studies suggest a role for lysophosphatidic acid receptor-1 (LPA receptor) in fibrosis. We investigated the therapeutic potential in systemic sclerosis (SSc) of a new orally active selective LPA receptor antagonist using dermal fibroblasts from patients and animal model of skin fibrosis.

Experimental Approach: Dermal fibroblast and skin biopsies from SSs patients were used. Read More

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http://dx.doi.org/10.1111/bph.15190DOI Listing

Brain control of appetite during sickness.

Br J Pharmacol 2020 Jul 5. Epub 2020 Jul 5.

Faculty of Biology, Medicine and Health, School of Medical Sciences, University of Manchester, Manchester, United Kingdom.

Given the high-energy requirements to sustain immune responses and healing processes, it is intriguing that lack of appetite (i.e. anorexia) is a cardinal feature of sickness behaviour. Read More

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http://dx.doi.org/10.1111/bph.15189DOI Listing

Heterologous expression of concatenated nicotine acetylcholine receptors: pros and cons of subunit concatenation and recommendations for construct designs.

Br J Pharmacol 2020 Jul 5. Epub 2020 Jul 5.

Brain and Mind Centre, 2Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW, 2006, Australia.

Background And Purpose: Concatenation of Cys-loop receptor subunits is a commonly used technique to ensure experimental control of receptor assembly. However, we recently demonstrated that widely used constructs did not lead to the expression of uniform pools of ternary and more complex receptors. The aim was therefore to identify viable strategies for designing concatenated constructs that would allow strict control of resultant receptor pools. Read More

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http://dx.doi.org/10.1111/bph.15188DOI Listing

Neuro-Oxysterols and Neuro-Sterols as Ligands to Nuclear Receptors, G Protein-Coupled Receptors, Ligand-Gated Ion Channels and other Protein Receptors.

Br J Pharmacol 2020 Jul 4. Epub 2020 Jul 4.

Swansea University Medical School, ILS1 Building, Singleton Park, Swansea, SA2 8PP, Wales, UK.

The brain is the most cholesterol rich organ in the body containing about 25% of the body's free cholesterol. Cholesterol cannot pass the blood brain barrier and be imported or exported, instead it is synthesised in situ and metabolised to oxysterols, oxidised forms of cholesterol, which can pass the blood brain barrier. 24S-Hydroxycholesterol is the dominant oxysterol in brain after parturition but during development a myriad of other oxysterols are produced which persist as minor oxysterols after birth. Read More

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http://dx.doi.org/10.1111/bph.15191DOI Listing

Outside In: Roles of Complement in Autophagy.

Br J Pharmacol 2020 Jul 4. Epub 2020 Jul 4.

Section of Medical Protein Chemistry, Department of Translational Medicine, Lund University, 214-28, Malmö, Sweden.

The complement system is a well-characterised cascade of extracellular serum proteins that is activated by pathogens and unwanted waste material. Products of activated complement signal to host cells via cell-surface receptors, illicting responses such as removal of the stimulus by phagocytosis. The complement system therefore functions as a warning system, resulting in removal of unwanted material. Read More

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http://dx.doi.org/10.1111/bph.15192DOI Listing

Interactions between cannabidiol and Δ -tetrahydrocannabinol in modulating seizure susceptibility and survival in a mousae model of Dravet syndrome.

Br J Pharmacol 2020 Jul 1. Epub 2020 Jul 1.

Brain and Mind Centre, The University of Sydney, Sydney, Australia.

Background And Purpose: Extracts from the cannabis plant can dramatically improve the health of children suffering from refractory epilepsies such as Dravet syndrome. These extracts typically contain cannabidiol (CBD), a phytocannabinoid with well-documented anticonvulsant effects, but may also contain Δ -tetrahydrocannabinol (Δ -THC). It is unclear whether the presence of Δ -THC modulates the anticonvulsant efficacy of CBD. Read More

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http://dx.doi.org/10.1111/bph.15181DOI Listing

A marine fungus-derived nitrobenzoyl sesquiterpenoid suppresses RANKL-induced osteoclastogenesis and attenuates inflammatory bone destruction.

Br J Pharmacol 2020 Jun 30. Epub 2020 Jun 30.

Laboratory of Anti-inflammatory and Immunomodulatory Pharmacology, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China.

Background And Purpose: Osteoclasts are unique cells to absorb bone, targeting osteoclast differentiation is a therapeutic strategy for osteolytic diseases. Marine natural products have already become important sources of new drugs. Naturally occurring nitrobenzoyl sesquiterpenoids (NSs), first identified from marine fungi in 1998, are bioactive compounds with a special structure, but their pharmacological functions are largely unknown. Read More

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http://dx.doi.org/10.1111/bph.15179DOI Listing

Translational approach to understanding momentary factors associated with alcohol consumption.

Br J Pharmacol 2020 Jun 30. Epub 2020 Jun 30.

Department of Informatics, Graduate School of Integrated Science and Technology, Shizuoka University, Japan.

Multiple inter- and intra-individual factors underlie variability in drinking motives, challenging clinical translatability of animal research and limiting treatment success of substance-use related problems. Intra-individual variability refers to time-dependent continuous and discrete changes within the individual, and in substance-use research is studied as momentary variation in the internal states (craving, stressed, anxious, impulsive, tired) and response to external triggers (stressors, drug-associated environmental cues, social encounters). These momentary stimuli have a direct impact on behavioural decisions, and may be triggers and predictors of substance consumption; they also present potential targets for real-time behavioural and pharmacological interventions. Read More

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http://dx.doi.org/10.1111/bph.15180DOI Listing

Inhibition of Bruton's tyrosine kinase regulates macrophage NF-κB and NLRP3 inflammasome activation in metabolic inflammation.

Br J Pharmacol 2020 Jul 1. Epub 2020 Jul 1.

William Harvey Research Institute, Queen Mary University of London, London, United Kingdom.

Background And Purpose: Currently there are limited medicines available for the treatment of metabolic inflammation in diseases such as obesity and type 2 diabetes (T2D). Although initially associated with B-ells, Bruton's tyrosine kinase (BTK) is present in a wide variety of cells including monocytes and macrophages, and has been implicated in the regulation of the NF-κB and NLRP3 inflammasome activity.

Experimental Approach: Using in vivo models of chronic inflammation [high-fat-diet (HFD) feeding] and in vitro assays in primary murine and human macrophages we investigated if ibrutinib, an FDA approved medicine that targets BTK, may represent a novel anti-inflammatory drug for the use in treating metabolic inflammation. Read More

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http://dx.doi.org/10.1111/bph.15182DOI Listing

A Systematic Review of Minor Phytocannabinoids with Promising Neuroprotective Potential.

Br J Pharmacol 2020 Jul 1. Epub 2020 Jul 1.

Division of Medical Sciences & Graduate Entry Medicine, School of Medicine, University of Nottingham, Royal Derby Hospital, DE22 3DT, United Kingdom.

Embase and Pubmed were systematically searched for articles addressing the neuroprotective properties of phytocannabinoids, aside from cannabidiol and Δ -tetrahydrocannabinol, including Δ -tetrahydrocannabinolic acid (Δ -THCA), Δ -tetrahydrocannabivarin (Δ -THCV), cannabidiolic acid (CBDA), cannabidivarin (CBDV), cannabichromene (CBC), cannabichromenic acid (CBCA), cannabichromevarin (CBCV), cannabigerol (CBG), cannabigerolic acid (CBGA), cannabigerivarin (CBGV), cannabigerovarinic acid (CBGVA), cannabichromevarinic acid (CBCVA) cannabidivarinic acid (CBDVA) and cannabinol (CBN). Out of 2,341 studies, 31 articles met inclusion criteria. CBG (range 5 mg. Read More

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http://dx.doi.org/10.1111/bph.15185DOI Listing

Inhibition of heparanase protects against pancreatic beta cell death in streptozotocin-induced diabetic mice via reducing intra-islet inflammatory cell infiltration.

Br J Pharmacol 2020 Jul 1. Epub 2020 Jul 1.

Key Laboratory of Human Functional Genomics of Jiangsu Province, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, 211166, China.

Background And Purpose: Intra-islet heparan sulfate (HS) plays an important role in the maintenance of the pancreatic islet function. The aim of this study was to investigate the effect mechanism of HS loss on the functioning of islets in diabetic mice.

Experimental Approach: The hypoglycemic effect of a heparanase inhibitor, OGT2115, was tested in a streptozotocin-induced diabetic mice model. Read More

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http://dx.doi.org/10.1111/bph.15183DOI Listing

Human skin models: from healthy to disease mimetic systems characteristics and applications.

Br J Pharmacol 2020 Jul 1. Epub 2020 Jul 1.

LAQV, REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Portugal, Rua de Jorge Viterbo Ferreira, 228, 4050-313, Porto, Portugal.

Skin drug delivery is an emerging route in the drug development, thus leading to an urgent need to understand the behaviour of active pharmaceutical ingredients within the skin. Given the skin barrier properties as one of the first body's natural defence systems, it can act as an obstacle to the successful outcome of a skin drug therapy. To unravel the mechanisms underlying this barrier, reductionist strategies have designed several models with different levels of complexity, using non-biological and biological components. Read More

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http://dx.doi.org/10.1111/bph.15184DOI Listing

The many mechanisms of action of Chloroquine: to use or not to use (in COVID-19) that is the question.

Br J Pharmacol 2020 Aug 30;177(15):3361-3362. Epub 2020 Jun 30.

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

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http://dx.doi.org/10.1111/bph.15177DOI Listing

MULTI-ANGLE DEVELOPMENT OF THERAPEUTIC METHODS FOR ALZHEIMER'S DISEASE.

Authors:
Minako Hoshi

Br J Pharmacol 2020 Jun 26. Epub 2020 Jun 26.

Department for Brain and Neurodegenerative Disease Research, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation at Kobe.

Recent clinical trial results support the idea that treatment based on the so-called amyloid hypothesis is a promising approach in Alzheimer's disease (AD), but actually developing effective treatments for AD remains highly challenging. The discovery that neuron-specific sodium pump activity is impaired in AD and other neurodegenerative diseases such as Parkinson's disease has suggested a role for the sodium pump in the pathogenesis of these diseases. This opens up new possibilities for intervention, such as inhibiting the aberrant interaction of the sodium pump with the disease-specific ligand(s), or activating the sodium pump itself or its downstream signaling. Read More

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http://dx.doi.org/10.1111/bph.15174DOI Listing

The role of complement in arterial hypertension and hypertensive end organ damage.

Br J Pharmacol 2020 Jun 25. Epub 2020 Jun 25.

III. Department of Medicine, University Hospital Hamburg-Eppendorf, Hamburg.

Increasing evidence indicates that hypertension and hypertensive end organ damage are not only mediated by hemodynamic injury but that inflammation also plays an important role. The complement system protects the host from a hostile microbial environment and maintains tissue and cell integrity through the elimination of altered or dead cells. As an important effector arm of innate immunity, it plays also central roles in the regulation of adaptive immunity. Read More

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http://dx.doi.org/10.1111/bph.15171DOI Listing

Regulation of smooth muscle contraction by monomeric non-RhoA GTPases.

Br J Pharmacol 2020 Jun 24. Epub 2020 Jun 24.

Department of Urology, University Hospital, LMU Munich, Munich, Germany.

Smooth muscle contraction in the cardiovascular system, airways, prostate, and lower urinary tract is involved in pathophysiology and medical treatment of widespread diseases, including cardiovascular diseases, obstructive lung diseases, and lower urinary tract symptoms, which are associated with high prevalence and mortality. In line with the prominent clinical role of smooth muscle tone, molecular mechanisms of smooth muscle contraction were subject of extensive research. At intracellular level, contraction is promoted by three widely accepted signaling pathways, shared by all smooth muscle-rich organs, and including the monomeric GTPase RhoA. Read More

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http://dx.doi.org/10.1111/bph.15172DOI Listing
June 2020
4.842 Impact Factor

Oxiapoptophagy: a type of cell death induced by some oxysterols.

Br J Pharmacol 2020 Jun 24. Epub 2020 Jun 24.

Univ. Bourgogne Franche-Comté, Team 'Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism' EA 7270/Inserm, Dijon, France.

Oxysterols are oxidized forms of cholesterol generated from cholesterol either by auto-oxidation, enzymatic processes or both. Some of them (7-ketocholesterol, 7β-hydroxycholesterol, 24(S)-hydroxycholesterol), when used at cytotoxic concentrations on different cell types from different species (mesenchymal bone marrow cells, monocytic cells, nerve cells), induce a type of cell death associated with OXIdative stress and several characteristics of APOPTOsis and autoPHAGY, defined as oxiapoptophagy. Oxidative stress is associated with overproduction of reactive oxygen species, increased antioxidant enzyme activities, lipid peroxidation and protein carbonylation. Read More

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http://dx.doi.org/10.1111/bph.15173DOI Listing

Sensitization of mGluR-mediated pain behavior via NGF- and A-kinase anchoring protein 5-dependent phosphorylation of TRPV1 under inflammatory conditions.

Br J Pharmacol 2020 Jun 24. Epub 2020 Jun 24.

Department of Pharmacology, School of Medicine, Kanazawa Medical University, Uchinada, Ishikawa, 920-0293, Japan.

Background And Purpose: Glutamate and metabotropic glutamate receptors on primary sensory neurons play a pivotal role in modulating pain sensitivity. However, it is unclear how inflammation affects mGluR-mediated nociceptive responses. We therefore investigated the effects of mGluR1/5 agonists on pain-related behavior under persistent inflammation and explored the underlying mechanisms. Read More

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http://dx.doi.org/10.1111/bph.15176DOI Listing

A chalcone derivative, 1m-6, exhibits atheroprotective effects by increasing cholesterol efflux and reducing inflammation-induced endothelial dysfunction.

Br J Pharmacol 2020 Jun 24. Epub 2020 Jun 24.

Division of Cardiology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, 11490, Taiwan.

Background And Purpose: Atherosclerosis, resulting from lipid dysregulation and vascular inflammation, causes atherosclerotic cardiovascular disease (ASCVD), which contributes to morbidity and mortality worldwide. Chalcone and its derivatives possess several beneficial properties, including anti-inflammatory, antioxidant, and antitumor activity with unknown cardioprotective effects. We aimed to develop an effective chalcone derivative with antiatherogenic potential. Read More

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http://dx.doi.org/10.1111/bph.15175DOI Listing

Correction.

Authors:

Br J Pharmacol 2020 Jul;177(14):3357

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http://dx.doi.org/10.1111/bph.15150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312412PMC

Novel Approach for Low-Dose Pulmonary Delivery of Hydroxychloroquine in COVID-19.

Br J Pharmacol 2020 Jun 19. Epub 2020 Jun 19.

Department of Pharmaceutical Sciences, School of Pharmacy, Temple University, 3307 North Broad Street, Philadelphia, PA, 19140.

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http://dx.doi.org/10.1111/bph.15167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7323163PMC

Integrins meet complement: the evolutionary tip of an iceberg orchestrating metabolism and immunity.

Br J Pharmacol 2020 Jun 19. Epub 2020 Jun 19.

Complement and Inflammation Research Section (CIRS), National Heart, Lung and Blood Institute, Bethesda, MD, USA.

Immunologists have recently realized that there is more to the classic innate immune sensor systems than just mere protection against invading pathogens. It is becoming increasingly clear that such sensors, including the inflammasomes, toll-like receptors and the complement system, are heavily involved in the regulation of basic cell physiological processes and particularly those of metabolic nature. In fact, their 'non-canonical' activities make sense as no system directing immune cell activity can perform such task without the need for energy. Read More

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http://dx.doi.org/10.1111/bph.15168DOI Listing

Statins: Could an old friend help the fight against COVID-19?

Br J Pharmacol 2020 Jun 19. Epub 2020 Jun 19.

Cellular and Molecular Biology in Renal and Vascular Pathology Laboratory, Fundación Instituto de Investigación Sanitaria-Fundación Jiménez Díaz-Universidad Autónoma Madrid, 28040, Madrid, Spain.

COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has overwhelmed Healthcare Systems requiring the rapid development of treatments, at least, to reduce COVID-19 severity. Drug repurposing offers a fast track. Here, we discuss the potential beneficial effects of statins in COVID-19 patients based on evidence that they may target virus receptors, replication, degradation and downstream responses in infected cells, addressing both basic research and epidemiological information. Read More

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http://dx.doi.org/10.1111/bph.15166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7323198PMC

CB1 receptor-dependent TRPV1 desensitisation contributes to the analgesic effect of dipyrone in sensitised primary sensory neurons.

Br J Pharmacol 2020 Jun 19. Epub 2020 Jun 19.

Department of Structural and Functional Biology, Institute of Biology, CP 6109, University of Campinas - UNICAMP, ZIP code: 13083-970, Campinas, Sao Paulo, Brazil.

Background And Purpose: While dipyrone is a widely used analgesic, its mechanism of action is not completely understood. Recently we have reported that the dipyrone metabolite 4-aminoantipirine (4-AA) reduces prostaglandin E (PGE )-induced pain-related behaviour through the cannabinoid type 1 (CB1) receptor. Here, we ascertained, in naive and PGE -induced "inflamed" conditions, both in vivo and in vitro, the molecular mechanisms involved in the 4-AA-induced analgesic effects. Read More

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http://dx.doi.org/10.1111/bph.15170DOI Listing

Multifunctional Opioid Receptor Agonism and Antagonism by a Novel Macrocyclic Tetrapeptide Prevents Reinstatement of Morphine-Seeking Behavior.

Br J Pharmacol 2020 Jun 19. Epub 2020 Jun 19.

Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville, FL, 32610.

Background And Purpose: The macrocyclic tetrapeptide natural product CJ-15,208 (cyclo[Phe-D-Pro-Phe-Trp]) is a multifunctional mu-opioid receptor (MOPr) and kappa-opioid receptor (KOPr) agonist and KOPr antagonist that produces antinociception and prevents stress-induced reinstatement of extinguished cocaine-conditioned place preference (CPP). We hypothesized that an analog of CJ-15,208, cyclo[Pro-Sar-Phe-D-Phe], would demonstrate multifunctional MOPr and KOPr ligand activity, producing potent antinociception with fewer liabilities than selective MOPr agonists while preventing both drug- and stress-induced reinstatement of morphine-CPP.

Experimental Approach: The opioid receptor agonist and antagonist activity of cyclo[Pro-Sar-Phe-D-Phe] was characterized after intracerebroventricular (i. Read More

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http://dx.doi.org/10.1111/bph.15165DOI Listing

Spinal HSP27 participates in PDGFRβ-mediated morphine tolerance through PI3K/Akt and p38 MAPK signaling pathways.

Br J Pharmacol 2020 Jun 19. Epub 2020 Jun 19.

Department of Anesthesiology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.

Background And Purpose: The development of antinociceptive morphine tolerance is a clinically intractable problem. Previous studies clarified the pivotal roles of platelet-derived growth factor (PDGF) and its receptor PDGFRβ in morphine tolerance. Herein, we investigated the role of spinal heat shock protein 27 (HSP27) in morphine tolerance and its relationship with PDGFRβ activation. Read More

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http://dx.doi.org/10.1111/bph.15169DOI Listing

Mechanism of action of SNF472, a novel calcification inhibitor to treat vascular calcification and calciphylaxis.

Br J Pharmacol 2020 Jun 18. Epub 2020 Jun 18.

Sanifit Therapeutics, Palma, Spain.

Background And Purpose: No therapy is approved for vascular calcification or calcific uremic arteriolopathy (calciphylaxis), which increase mortality and morbidity in patients undergoing dialysis. Deposition of hydroxyapatite (HAP) crystals in arterial walls is the common pathophysiologic mechanism. These experiments examined the mechanism of action of SNF472 to reduce HAP deposition in arterial walls. Read More

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http://dx.doi.org/10.1111/bph.15163DOI Listing

Harnessing inflammation resolving-based therapeutic agents to treat pulmonary viral infections: What can the future offer to COVID-19?

Br J Pharmacol 2020 Jun 18. Epub 2020 Jun 18.

Laboratorio de Imunofamacologia, Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.

Inflammation is generally accepted as a component of the host defence system and a protective response in the context of infectious diseases. However, altered inflammatory responses can contribute to disease in infected individuals. Many endogenous mediators that drive the resolution of inflammation are now known. Read More

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http://dx.doi.org/10.1111/bph.15164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7323156PMC

The ventral pallidum and relapse in alcohol seeking.

Br J Pharmacol 2020 Jun 17. Epub 2020 Jun 17.

School of Psychology, UNSW Sydney, Sydney, NSW, Australia.

Alcohol-use disorders are chronically relapsing conditions characterized by cycles of use, abstinence and relapse. The ventral pallidum (VP) is a key node in the neural circuits controlling relapse to alcohol seeking and a key target of pharmacotherapies for relapse prevention. There has been a significant increase in our understanding of the molecular, anatomical, pharmacological and functional properties of the ventral pallidum, laying foundations for a new understanding of its role in relapse to alcohol seeking and motivation. Read More

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http://dx.doi.org/10.1111/bph.15160DOI Listing

The coffee ingredients caffeic acid (CA) and caffeic acid phenylethyl ester (CAPE) protect against irinotecan induced leukopenia and oxidative stress response.

Br J Pharmacol 2020 Jun 16. Epub 2020 Jun 16.

Department of Internal Medicine I, University Hospital Bonn, 53127, Bonn, Germany.

Background And Purpose: Irinotecan, a drug used in colorectal cancer therapy is metabolized by glucuronidation involving different UDP-glucuronosyltransferase (UGT)1A isoforms, which leads to facilitated elimination from the body. Individuals homozygous for the genetic variants UGT1A1*28 (Gilbert syndrome) and UGT1A7*3 are more susceptible to irinotecan drug side effects such as severe diarrhea and leukopenia. Aim of this study was to study the protective effects and active constituents of coffee during irinotecan therapy using humanized transgenic (htg)UGT1A-WT and htgUGT1A-SNP (carry UGT1A1*28 and UGT1A7*3 polymorphisms) mice. Read More

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http://dx.doi.org/10.1111/bph.15162DOI Listing

Transient stimulation of TRPV4-expressing keratinocytes promotes hair follicle regeneration in mice.

Br J Pharmacol 2020 Jun 16. Epub 2020 Jun 16.

Department of Anesthesiology, the Center for the Study of Itch & Sensory Disorders, Washington University School of Medicine, St. Louis, MO, 63110, USA.

Background And Purpose: Hair follicle (HF) telogen to anagen transition results in a break in cellular quiescence of the HF stem cells, which subsequently promotes HF regeneration. Many critical molecules and signaling pathways are involved in HF cycle progression. Transient receptor potential vanilloid 4 (TRPV4) is a polymodal sensory transducer that regulates various cutaneous functions under both normal and disease conditions. Read More

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http://dx.doi.org/10.1111/bph.15161DOI Listing

Therapeutic implications of the PP2A/MET signalling axis in doxorubicin-induced cardiotoxicity and antitumour properties.

Br J Pharmacol 2020 Jun 14. Epub 2020 Jun 14.

Cancer Unit for Research on Novel Therapeutic Targets, Oncohealth Institute, IIS-Fundación Jiménez Díaz-UAM, Madrid, Spain.

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http://dx.doi.org/10.1111/bph.15130DOI Listing

Sirtuin 3-mediated deacetylation of acyl-CoA synthetase family member 3 by protocatechuic acid attenuates nonalcoholic fatty liver disease.

Br J Pharmacol 2020 Jun 10. Epub 2020 Jun 10.

Department of Pharmacology, Dalian Medical University, Dalian, 116044, China.

Background And Purpose: Hepatic fatty acid metabolism disorder, a key pathogenic mechanism underlying nonalcoholic fatty liver disease (NAFLD), is associated with the hyperacetylation of mitochondrial enzymes. Acyl-CoA synthetase family member 3 (ACSF3), which is involved in the regulation of fatty acid metabolism, was predicted to contain lysine acetylation sites related to the mitochondrial deacetylase sirtuin 3 (SIRT3). The purpose of this study was to explore the underlying mechanism by which SIRT3 deacetylates ACSF3 in NAFLD and the protective effect of the natural phenolic compound protocatechuic acid (PCA) against fatty acid metabolism disorder via the SIRT3/ACSF3 pathway. Read More

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http://dx.doi.org/10.1111/bph.15159DOI Listing
June 2020
4.842 Impact Factor

Artesunate interacts with the vitamin D receptor to reverse sepsis-induced immunosuppression in a mouse model via enhancing autophagy.

Br J Pharmacol 2020 Jun 10. Epub 2020 Jun 10.

Medical Research Center, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.

Background And Purpose: Immunosuppression is the predominant cause of mortality for sepsis because of failure to eradicate pathogens. No effective and specific drugs capable of reversing immunosuppression are clinically available. Evidences implicate the involvement of the vitamin D receptor (NR1I1) in sepsis-induced immunosuppression. Read More

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http://dx.doi.org/10.1111/bph.15158DOI Listing

Pro-resolving mediator protectin D1 promotes epimorphic regeneration by controlling immune cell function in vertebrates.

Br J Pharmacol 2020 Jun 10. Epub 2020 Jun 10.

IRMB, INSERM, Univ Montpellier, CHU Montpellier, Montpellier, France.

Background And Purpose: Specialized pro-resolving mediators (SPMs) are a family of lipids controlling the resolution of inflammation and playing a role in many processes including organ protection and tissue repair. While SPMs are potent bioactive molecules in vivo, their role in epimorphic regeneration of organs in vertebrates has not been tested. Using the zebrafish larva as a robust regenerative vertebrate system, we studied the role of the SPM neuroprotectin/protectin D1 (PD1) during the caudal fin fold regeneration. Read More

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http://dx.doi.org/10.1111/bph.15156DOI Listing

The potential of cannabidiol in the COVID-19 pandemic: a hypothesis letter.

Br J Pharmacol 2020 Jun 10. Epub 2020 Jun 10.

Department of Clinical Medicine and Surgery, University of Naples "Federico II", Naples, Italy.

Identifying candidate drugs effective in the new coronavirus disease 2019 (Covid-19) is crucial, pending a vaccine against SARS-CoV2. We suggest the hypothesis that Cannabidiol (CBD), a non-psychotropic phytocannabinoid, has the potential to limit the severity and progression of the disease for several reasons: 1) High-CBD Cannabis Sativa extracts are able to downregulate the expression of the two key receptors for SARS-CoV2 in several models of human epithelia 2) CBD exerts a wide range of immunomodulatory and anti-inflammatory effects and it can mitigate the uncontrolled cytokine production featuring Acute Lung Injury 3) Being a PPARγ agonist, it can display a direct antiviral activity 4) PPARγ agonists are regulators of fibroblast/myofibroblast activation and can inhibit the development of pulmonary fibrosis, thus ameliorating lung function in recovered patients. We hope our hypothesis, corroborated by several preclinical evidence, will inspire further targeted studies to test CBD as a support drug against the COVID-19 pandemic. Read More

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http://dx.doi.org/10.1111/bph.15157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7300643PMC

Retraction.

Authors:

Br J Pharmacol 2020 Jul 20;177(13):3123. Epub 2020 May 20.

Retraction: Spagnuolo, R., Recalcati, S., Tacchini, L. Read More

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http://dx.doi.org/10.1111/bph.15097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7279991PMC

Δ -Tetrahydrocannabinolic acid alleviates collagen-induced arthritis: Role of PPARγ and CB receptors.

Br J Pharmacol 2020 Jun 8. Epub 2020 Jun 8.

Maimonides Biomedical Research Institute of Córdoba, University of Córdoba, Córdoba, Spain.

Background And Purpose: Δ -Tetrahydrocannabinolic acid (Δ -THCA-A), the precursor of Δ -THC, is a non-psychotropic phytocannabinoid that shows PPARγ agonist activity. Here, we investigated the ability of Δ -THCA-A to modulate the classic cannabinoid CB and CB receptors and evaluated its anti-arthritis activity in vitro and in vivo.

Experimental Approach: Cannabinoid receptors binding and intrinsic activity, as well as their downstream signalling, were analysed in vitro and in silico. Read More

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http://dx.doi.org/10.1111/bph.15155DOI Listing

Recombinant Thrombomodulin Protects Against Lipopolysaccharide-induced Acute Respiratory Distress Syndrome Via Preservation of Pulmonary Endothelial Glycocalyx.

Br J Pharmacol 2020 Jun 4. Epub 2020 Jun 4.

Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.

Background And Purpose: Endothelial glycocalyx (eGC) disruption is causally related to microvascular endothelial dysfunction, a characteristic of sepsis-induced acute respiratory distress syndrome (ARDS). Recombinant human thrombomodulin (rhTM) reportedly attenuates vascular endothelial injuries, but the underlying mechanism remains elusive. Here, we investigated the structural basis and molecular mechanisms of rhTM effects on vascular endothelial injury in sepsis. Read More

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http://dx.doi.org/10.1111/bph.15153DOI Listing

A lesson from a saboteur: High-MW kininogen impact in coronavirus-induced disease 2019.

Br J Pharmacol 2020 Jun 4. Epub 2020 Jun 4.

Department of Pharmacy (DIFARMA), University of Salerno, Fisciano, Italy.

The newly identified coronavirus SARS-CoV-2 that spread from China is causing the pandemic COVID-19 with a fatality rate from 5-15%. It causes fever, cough, myalgia, fatigue up to dyspnoea, responsible for hospitalization and artificial oxygenation. SARS-CoV-2 infects human cells using ACE2, the transmembrane protease serine 2 (TMPRSS2) and the SARS-CoV-2 main protease (M ). Read More

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http://dx.doi.org/10.1111/bph.15154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7300552PMC

Amyotrophic lateral sclerosis (ALS), cancer, autoimmunity and metabolic disorders: An unsolved tantalizing challenge.

Br J Pharmacol 2020 Jun 4. Epub 2020 Jun 4.

Centro de Investigación en Red de Enfermedades Neurodegenerativas, CIBERNED, Instituto Carlos III, Madrid, Spain.

Amyotrophic lateral sclerosis (ALS) commonly referred to as motor neurone disease, is a neurodegenerative disease of unknown pathogenesis that progresses rapidly and has attracted an increased amount of scholarly interest in recent years. The current conception of amyotrophic lateral sclerosis has transitioned into a more complex theory in which individual genetic risk, ageing and environmental factors interact, leading to disease onset in subjects in whom the sum of these factors reach a determined threshold. Based on this conceptualization, the environmental conditions, particularly those that are potentially modifiable, are becoming increasingly relevant. Read More

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http://dx.doi.org/10.1111/bph.15151DOI Listing

Ethaninidothioic acid (R5421) is not a selective inhibitor of platelet phospholipid scramblase activity.

Br J Pharmacol 2020 Jun 4. Epub 2020 Jun 4.

Department of Pharmacology, University of Cambridge, Cambridge, UK.

Background And Purpose: Ethaninidothioic acid (R5421) has been used as a scramblase inhibitor to determine the role of phospholipid scrambling across a range of systems including platelet procoagulant activity. The selectivity of R5421 has not been thoroughly studied. Here, we characterised the effects of R5421 on platelet function and its suitability for use as a scramblase inhibitor. Read More

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http://dx.doi.org/10.1111/bph.15152DOI Listing

Silencing of spontaneous activity at α4β1/3δ GABA receptors in hippocampal granule cells reveals different ligand pharmacology.

Br J Pharmacol 2020 Jun 2. Epub 2020 Jun 2.

Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100, Copenhagen, Denmark.

Background And Purpose: The δ-subunit containing GABA receptors, α β δ and α β δ in dentate gyrus granule cells (DGGCs) are known to exhibit both spontaneous channel openings (i.e constitutive activity) and agonist-induced current. The functional implications of spontaneous gating is unclear. Read More

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http://dx.doi.org/10.1111/bph.15146DOI Listing

Metformin mitigates gastrointestinal radiotoxicity and radiosensitises P53 mutation colorectal tumours via optimising autophagy.

Br J Pharmacol 2020 May 30. Epub 2020 May 30.

State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Rocket Force Medicine, Third Military Medical University (Army Medical University), Chongqing, China.

Background And Purpose: There is an urgent but unmet need for mitigating radiation-induced intestinal toxicity while radio sensitising tumours for abdominal radiotherapy. We aimed to investigate the effects of metformin on radiation-induced intestinal toxicity and radiosensitivity of colorectal tumours.

Experimental Approach: Acute and chronic histological injuries of the intestine from mice were used to assess radioprotection and IEC-6 cell line was used to investigate the mechanisms in vitro. Read More

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http://dx.doi.org/10.1111/bph.15149DOI Listing

Targeting TDP-43 proteinopathy with drugs and drug-like small molecules.

Authors:
Emanuele Buratti

Br J Pharmacol 2020 May 29. Epub 2020 May 29.

International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy.

Following the discovery of the involvement of the ribonucleoprotein TDP-43 in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD), a major research focus has been to develop treatments that can prevent or alleviate these disease conditions. One pharmacological approach has been to use TDP-43-based disease models to test small molecules and drugs already known to have some therapeutic effect in a variety of neurodegenerative conditions. In parallel, various disease models have been used to perform high-throughput screens of drugs and small compound libraries. Read More

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http://dx.doi.org/10.1111/bph.15148DOI Listing

BK channel subunits promote breast cancer development and modulate endocrine treatment response in pre-clinical models.

Br J Pharmacol 2020 May 28. Epub 2020 May 28.

Department of Pharmacology, Toxicology and Clinical Pharmacy, Institute of Pharmacy, University of Tuebingen, 72076, Tuebingen, Germany.

Background And Purpose: Pore-forming α subunits of the voltage- and Ca -activated K channel of big conductance (BKα) promote malignant phenotypes of breast tumour cells. Auxiliary subunits such as the leucine-rich repeat containing 26 (LRRC26) protein, also termed BKγ1, may be required to confer activation of BK currents at a depolarized resting membrane potential that frequently occur in an inexcitable tumour cell.

Experimental Approach: Anti-tumour effects of BKα loss were investigated in breast tumour-bearing MMTV-PyMT transgenic BKα knockout (KO) mice, primary MMTV-PyMT cell cultures, and in a syngeneic transplantation model of breast cancer (BC) derived thereof. Read More

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http://dx.doi.org/10.1111/bph.15147DOI Listing

Hypoxia-induced pulmonary hypertension - utilising experiments of nature.

Br J Pharmacol 2020 May 28. Epub 2020 May 28.

National Heart and Lung Institute (NHLI), Imperial College London, Hammersmith Hospital, Du Cane Road, London, W12 0NN, UK.

An increase in pulmonary artery pressure is a common observation in adult mammals exposed to global alveolar hypoxia. It is considered a maladaptive response that places an increased workload on the right ventricle. The mechanisms initiating and maintaining the elevated pressure are of considerable interest to understanding pulmonary vascular homeostasis. Read More

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http://dx.doi.org/10.1111/bph.15144DOI Listing