24,008 results match your criteria British journal of pharmacology[Journal]


Cannabinoid CB and CB receptor mechanisms underlie cannabis reward and aversion in rats.

Br J Pharmacol 2019 Feb 14. Epub 2019 Feb 14.

Molecular Targets and Medications Discovery Branch, Intramural Research Program, National Institute on Drug Abuse, 251 Bayview Blvd, Baltimore, MD, 21224, USA.

Background And Purpose: Endocannabinoids are critically involved in brain reward functions. This is generally believed to be mediated by activation of CB receptors, in large part due to their high density in the brain. However, the recent discovery of CB receptors (CB R) in the brain, particularly in midbrain dopamine neurons, has challenged this view and inspired us to re-examine the roles of both CB R and CB R in the effects of cannabis. Read More

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http://doi.wiley.com/10.1111/bph.14625
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http://dx.doi.org/10.1111/bph.14625DOI Listing
February 2019
1 Read

Modafinil protects hippocampal neurons by suppressing excessive autophagy and apoptosis in mice with sleep deprivation.

Br J Pharmacol 2019 Feb 14. Epub 2019 Feb 14.

Shanghai Key Laboratory of Compound Chinese Medicines, The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, 201203, Shanghai, China.

Background And Purpose: Sleep deprivation (SD) compromises learning and memory in both humans and animals, which can be reversed by administration of modafinil, a wake-promoting drug. Dysfunctional autophagy promotes the activation of apoptotic cascades, ultimately leading to an increased neuronal death, which can be alleviated by autophagy inhibitors. This study is aimed to investigate the alleviative effect and mechanism of modafinil on the excessive autophagy in hippocampus of mice with deficiency of learning and memory induced by SD. Read More

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http://doi.wiley.com/10.1111/bph.14626
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http://dx.doi.org/10.1111/bph.14626DOI Listing
February 2019
6 Reads

Trehalose as a Promising Therapeutic Candidate for the Treatment of Parkinson's Disease.

Br J Pharmacol 2019 Feb 14. Epub 2019 Feb 14.

Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Parkinson's disease (PD) is a progressive movement disorder resulting primarily from loss of nigrostriatal dopaminergic neurons. PD is characterized by the accumulation of protein aggregates and evidence suggests that aberrant protein deposition in dopaminergic neurons could be related to the dysregulation of the lysosomal autophagy pathway. The therapeutic potential of autophagy modulators has been reported in experimental models of PD. Read More

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http://dx.doi.org/10.1111/bph.14623DOI Listing
February 2019

Sex differences in mechanisms of arterial stiffness.

Br J Pharmacol 2019 Feb 14. Epub 2019 Feb 14.

Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA.

Arterial stiffness progressively increases with ageing and is an independent predictor of cardiovascular disease (CVD) risk. Evidence supports that there are sex differences in the time course of aging-related arterial stiffness and the associated CVD risk which increases disproportionately in postmenopausal women. The association between arterial stiffness and mortality is almost 2 fold higher in women versus men. Read More

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http://dx.doi.org/10.1111/bph.14624DOI Listing
February 2019

Neprilysin inhibition for pulmonary arterial hypertension: a randomized, double-blind, placebo-controlled, proof-of-concept trial.

Br J Pharmacol 2019 Feb 13. Epub 2019 Feb 13.

Dorset County Hospital NHS Foundation Trust, Williams Avenue, Dorchester, Dorset, DT1 2JY.

Background And Purpose: Pulmonary arterial hypertension (PAH) is an incurable, incapacitating disorder resulting from increased pulmonary vascular resistance, pulmonary arterial remodeling and right ventricular failure. In pre-clinical models, combination of a phosphodiesterase 5 inhibitor (PDE5i) with a neprilysin inhibitor augments natriuretic peptide bioactivity, promotes cyclic GMP signaling, and reverses the structural and hemodynamic deficits that characterize PAH. Herein, we conducted a randomized, double-blind, placebo-controlled trial to assess the efficacy and safety of repurposing the neprilysin inhibitor, racecadotril, in PAH. Read More

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http://dx.doi.org/10.1111/bph.14621DOI Listing
February 2019

Small-molecule inhibition of prostaglandin E receptor 2 impairs cyclooxygenase-associated malignant glioma growth.

Br J Pharmacol 2019 Feb 14. Epub 2019 Feb 14.

Division of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, Ohio, USA.

Background And Purpose: Induced cyclooxygenase-2 (COX-2) in malignant gliomas causes excessive synthesis of prostaglandin E2 (PGE ) that is thought to facilitate the brain tumor growth and invasion. However, which downstream PGE receptor subtype (i.e. Read More

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http://doi.wiley.com/10.1111/bph.14622
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http://dx.doi.org/10.1111/bph.14622DOI Listing
February 2019
1 Read

β-adrenoceptor activation impacts galectin-3 as a biomarker and therapeutic target in heart disease.

Br J Pharmacol 2019 Feb 12. Epub 2019 Feb 12.

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

Myocardial fibrosis is a key histopathological component that drives the progression of heart disease leading to heart failure and forms a therapeutic target. Recent preclinical and clinical studies have implicated galectin-3 (Gal-3) as a pro-fibrotic molecule and a biomarker of heart disease and fibrosis. However, our knowledge is poor on the mechanism(s) that determine the blood level or regulate cardiac expression of Gal-3. Read More

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http://dx.doi.org/10.1111/bph.14620DOI Listing
February 2019

Histamine in the kidneys: What is its role in renal pathophysiology?

Br J Pharmacol 2019 Feb 11. Epub 2019 Feb 11.

Department of Scienza e Tecnologia del Farmaco, University of Turin, Via P. Giuria 9, 10125, Turin, Italy.

Starting from the histamine role in the renal haemodynamic, over time, spare evidence suggested a wider range of action on renal function and renewed the interest on the pathophysiological role of histamine in the kidney. This review intends to provide an up-to-date focus on this topic. According to the intrarenal production of histamine and the renal presence of its receptors, the histaminergic machinery appears to be well suited. Read More

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http://dx.doi.org/10.1111/bph.14619DOI Listing
February 2019
1 Read

Adrenoceptor regulation of mTOR in muscle and adipose tissue.

Br J Pharmacol 2019 Feb 10. Epub 2019 Feb 10.

Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, Victoria, 3052, Australia.

A vital role of adrenoceptors in metabolism and energy balance has been well-documented in heart, skeletal muscle, and adipose tissue. It has been only recently demonstrated, however, that activation of mechanistic/mammalian target of rapamycin (mTOR) makes a significant contribution to various metabolic and physiological responses to adrenoceptor agonists. mTOR exists as two distinct complexes named mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2), and has been shown to play a critical role in protein synthesis, cell proliferation, hypertrophy, mitochondrial function, and glucose uptake. Read More

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http://dx.doi.org/10.1111/bph.14616DOI Listing
February 2019

Updates in the Function and Regulation of α -Adrenoceptors.

Br J Pharmacol 2019 Feb 10. Epub 2019 Feb 10.

Department of Pharmacology, Instituto de Biociências, UNESP, Rua Prof. Dr. Antônio Celso Wagner Zanin, 250, Botucatu, SP, Brazil, 18618-689.

α -Adrenoceptors (α -ARs) are seven transmembrane domain G-protein coupled receptors involved in numerous physiological functions controlled by the endogenous catecholamines noradrenaline and adrenaline and targeted by drugs useful in therapeutics. Three separate genes, whose products are named α -, α - and α -ARs, encode these receptors. Although the existence of multiple α -ARs has been acknowledged for almost 25 years, the specific functions regulated by each subtype are still largely unknown. Read More

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http://dx.doi.org/10.1111/bph.14617DOI Listing
February 2019

Microglial inflammation and phagocytosis in Alzheimer's disease: potential therapeutic targets.

Br J Pharmacol 2019 Feb 10. Epub 2019 Feb 10.

Alzheimer's Research UK Oxford Drug Discovery Institute, Nuffield Department of Medicine, University of Oxford, UK.

One of the largest unmet medical needs is a disease-modifying treatment for Alzheimer's disease (AD). Recently the role of microglia in disease, particularly AD, has gained great interest, following the identification of several disease risk-associated genes that are highly expressed in microglia. Microglia play a critical homeostatic role in the brain, with neuroinflammatory and phagocytic mechanisms being of particular importance. Read More

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http://dx.doi.org/10.1111/bph.14618DOI Listing
February 2019
1 Read

The impact of dihydropyridine derivatives on the cerebral blood flow response to somatosensory stimulation and spreading depolarization.

Br J Pharmacol 2019 Feb 9. Epub 2019 Feb 9.

Department of Medical Physics and Informatics, Faculty of Medicine and Faculty of Science and Informatics, University of Szeged; Koranyi fasor 9, H-6721, Szeged, Hungary.

Background And Purpose: A new class of heat shock protein co-inducer dihydropyridine derivatives devoid of calcium channel antagonist and vasodilator effects have been recently developed with the purpose to target neurodegeneration selectively. Here we set out to evaluate the action of one of these novel compounds LA1011 on neurovascular coupling in the ischemic rat cerebral cortex. As a reference, we applied nimodipine, a well-known calcium channel antagonist, vasodilator dihydropyridine compound. Read More

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http://dx.doi.org/10.1111/bph.14611DOI Listing
February 2019

An osteoclastogenesis system, the RANKL/RANK signaling pathway contributes to aggravated allergic inflammation.

Br J Pharmacol 2019 Feb 9. Epub 2019 Feb 9.

Division of Food and Pharmaceutical Engineering, Biochip Research Center and Inflammatory Diseases Research Center, Hoseo University, Asan, Chungnam, 31499, Republic of Korea.

Background And Purpose: As an osteoclast differentiation factor, receptor activator of nuclear factor-κB ligand (RANKL) is produced by various immune cells and is suspected in the pathogenesis of osteoporosis and inflammation. Although RANKL isbroadly expressed in most immune cells and tissues, it is not clear how this might affect allergic inflammation.

Experimental Approach: The roles of RANKL in allergic rhinitis (AR) were analyzed in an ovalbumin (OVA)-induced AR animal model, human subjects, and ahuman mast cell. Read More

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http://dx.doi.org/10.1111/bph.14615DOI Listing
February 2019
2 Reads

Semaphorin 3E attenuates intestinal inflammation through the regulation of the communication between splenic CD11C and CD4 CD25 T cells.

Br J Pharmacol 2019 Feb 8. Epub 2019 Feb 8.

Department of Immunology, University of Manitoba, Winnipeg, MB, Canada.

Background And Purpose: Alteration of the communication between the innate and adaptive immune cells is a hallmark of ulcerative colitis (UC). Semaphorin-3E (SEMA3E), a secreted guidance protein, regulates various immune responses.

Experimental Approach: We investigated SEMA3E expression in colonic biopsies of active UC patients and its mechanisms in Sema3e mice using a UC model of experimental colitis. Read More

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http://dx.doi.org/10.1111/bph.14614DOI Listing
February 2019

Cannabinoids differentially modulate the cortical information transmission through the sensorimotor or medial prefrontal basal ganglia circuits.

Br J Pharmacol 2019 Feb 8. Epub 2019 Feb 8.

Department of Pharmacology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), 48940, Leioa, Spain.

Background And Purpose: In the sensorimotor (SM) and medial prefrontal (mPF) basal ganglia (BG) circuits, the cortical information is transferred to the substantia nigra pars reticulata (SNr) through the hyperdirect trans-subthalamic pathway and through the direct and indirect trans-striatal pathways. The CB1 cannabinoid receptor, which is densely located in both BG circuits, may participate in the regulation of motor and motivational behaviours. Here, we investigated the modulation of cortico-nigral information transmission through the BG circuits by cannabinoids. Read More

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http://dx.doi.org/10.1111/bph.14613DOI Listing
February 2019

GSK2646264, a spleen tyrosine kinase inhibitor attenuates the release of histamine in ex vivo human skin.

Br J Pharmacol 2019 Feb 8. Epub 2019 Feb 8.

Respiratory TAU, GSK, Gunnels Wood Rd, Stevenage.

Background And Purpose: Chronic Spontaneous Urticaria presents as a heterogeneous syndrome characterised by wheals, angioedema or both for greater than six weeks. Spleen tyrosine kinase (SYK) mediates allergen-induced mast cell degranulation via the IgE signalling pathway, a central component of wheal formation and inflammation. In this study, we demonstrate that perfused or topically administered GSK2646264 dose dependently attenuates IgE-mediated histamine release from mast cells in an ex vivo human skin model. Read More

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http://dx.doi.org/10.1111/bph.14610DOI Listing
February 2019
1 Read

Pathology of white matter integrity in three major white matter fasciculi: A postmortem study of schizophrenia and treatment status.

Br J Pharmacol 2019 Feb 8. Epub 2019 Feb 8.

Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Birmingham, AL, 35294.

Background And Aims: Imaging studies have shown that people with schizophrenia exhibit abnormal connectivity termed "dysconnectivity" in several white matter tracts, including the cingulum bundle (CB), corpus callosum (CC), and arcuate fasciculus (AF). This study aimed to elucidate potential contributors to schizophrenia "dysconnectivity."

Experimental Approach: This study used Western blot analysis to compare protein levels of myelin basic protein (MBP), neurofilament heavy (NFH), autophagosome marker LC3, and microtubule marker α-tubulin in postmortem human CB, CC, AF in schizophrenia subjects (SZ; n=16) and matched controls (NC; n=15). Read More

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http://dx.doi.org/10.1111/bph.14612DOI Listing
February 2019

Hydrogen Sulfide Regulates Muscle RING Finger-1 Protein S-Sulfhydration at Cys44 to Prevent Cardiac Structural Damage in Diabetic Cardiomyopathy.

Br J Pharmacol 2019 Feb 7. Epub 2019 Feb 7.

Department of Pathophysiology, Harbin Medical University, Harbin, 150086, China.

Background And Purpose: Hydrogen sulfide (H S) plays important roles as a gasotransmitter in pathologies. Increasing E3 ubiquitin ligase muscle RING-finger-1 (MuRF1) expression may be involved in diabetic cardiomyopathy (DCM). This study was to investigate whether and how exogenous H S alleviates cardiac muscle degradation through modifications of MuRF1 S-sulfhydration in db/db mice. Read More

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http://dx.doi.org/10.1111/bph.14601DOI Listing
February 2019

Vasoactive Intestinal Peptide shapes first trimester placenta trophoblast, vascular and immune cell cooperation.

Br J Pharmacol 2019 Feb 6. Epub 2019 Feb 6.

Maternal and Fetal Health Research Centre, University of Manchester, Manchester Academic Health Sciences Centre, St. Mary's Hospital, Manchester, M13 9WL, UK.

Background And Purpose: Extravillous trophoblast cells (EVT) are responsible for decidual stromal invasion, vascular transformation and the recruitment and functional modulation of maternal leukocytes in the first trimester pregnant uterus. An early disruption of EVT function leads to placental insufficiency underlying pregnancy complications such as preeclampsia and fetal growth restriction. Vasoactive intestinal peptide (VIP) is a vasodilating and immune modulatory factor synthesized by trophoblast cells. Read More

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http://dx.doi.org/10.1111/bph.14609DOI Listing
February 2019
2 Reads

WHAT MAKES THE α -ADRENOCEPTOR GENE PRODUCT ASSUME A α -ADRENOCEPTOR PHENOTYPE?

Br J Pharmacol 2019 Feb 4. Epub 2019 Feb 4.

Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia.

The α -adrenoceptor is abundantly expressed in the lower urinary tract and is the principal therapeutic target for the symptomatic treatment of lower urinary tract symptoms in men. Prazosin has a lower affinity for the lower urinary tract α -adrenoceptor than α -adrenoceptors found in other parts of the body. This has led to the lower urinary tract α -adrenoceptor being subclassified as a α -adrenoceptor. Read More

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http://dx.doi.org/10.1111/bph.14599DOI Listing
February 2019

Cav3.2 calcium channel inhibition: a new target for colonic hypersensitivity associated with low-grade inflammation.

Br J Pharmacol 2019 Feb 4. Epub 2019 Feb 4.

Université Clermont Auvergne, INSERM, NEURO-DOL Basics & Clinical Pharmacology of Pain, F-63000, Clermont-Ferrand, France.

Background And Purpose: Abdominal pain associated with low-grade inflammation is frequently encountered in irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) during the remission phase. Current treatments are generally weakly effective. Therefore, new therapeutic approaches are needed. Read More

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http://doi.wiley.com/10.1111/bph.14608
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http://dx.doi.org/10.1111/bph.14608DOI Listing
February 2019
5 Reads

Function of cyclic AMP scaffolds in obstructive lung disease: Focus on epithelial-to-mesenchymal transition and oxidative stress.

Br J Pharmacol 2019 Feb 4. Epub 2019 Feb 4.

Department of Molecular Pharmacology, University of Groningen, The Netherlands.

Over the past decades, research has defined cyclic adenosine monophosphate (cAMP) as one of the central cellular nodes in sensing and integrating multiple pathways, and as a pivotal role player in lung pathophysiology. Obstructive lung disorders, such as chronic obstructive pulmonary disease (COPD), are characterized by a persistent and progressive airflow limitation, and by oxidative stress from endogenous and exogenous insults. The extent of airflow obstruction relies on the relative deposition of different constituents of the extracellular matrix - a process related to epithelial-to-mesenchymal transition, and which subsequently results in airway fibrosis. Read More

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http://dx.doi.org/10.1111/bph.14605DOI Listing
February 2019
1 Read

Drug interactions with dementia-related pathophysiological pathways worsen or prevent dementia.

Br J Pharmacol 2019 Feb 4. Epub 2019 Feb 4.

Univlille, INSERM, CHU de Lille, Degenerative and vascular cognitive disorders, Lille, F-59000.

Many risk factors are known to induce or precipitate dementia. Drugs acting via different mechanisms can modulate cognitive performance and exert either beneficial or deleterious effects on cognition through functional or neuropathological mechanisms. This review discusses the association between several classes of drugs and cognitive impairment and dementia risk. Read More

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http://dx.doi.org/10.1111/bph.14607DOI Listing
February 2019
1 Read

The histidine decarboxylase model of tic pathophysiology: A new focus on the H3R receptor.

Br J Pharmacol 2019 Feb 4. Epub 2019 Feb 4.

Department of Psychiatry, School of Medicine, Yale University, 34 Park Street, 333b, New Haven, CT, 06524.

Histamine dysregulation was implicated as a rare cause of Tourette syndrome and other tic disorders a decade ago by a landmark genetic study in a high-density family pedigree, which implicated a hypomorphic mutation in the histidine decarboxylase (Hdc) gene as a rare but high-penetrance genetic cause. Studies in Hdc knockout mice have confirmed that this mutation causes tic-relevant behavioral and neurochemical abnormalities that parallel what is seen in patients and thus validate the knockout as a potentially informative model of tic pathophysiology. Recent studies have focused on the potential role of the H3R histamine receptor in this model, and by association in tic disorders and related neuropsychiatric conditions. Read More

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http://doi.wiley.com/10.1111/bph.14606
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http://dx.doi.org/10.1111/bph.14606DOI Listing
February 2019
5 Reads

Mechanisms of Hypertension in Autoimmune Rheumatic Diseases.

Br J Pharmacol 2019 Feb 3. Epub 2019 Feb 3.

Department of Physiology & Biophysics, University of Mississippi Medical Center, Jackson, MS, 39216, US.

Patients with autoimmune rheumatic diseases including rheumatoid arthritis and systemic lupus erythematosus have an increased prevalence of hypertension. There is now a large body of evidence showing that the immune system is a key mediator in both human primary hypertension and in experimental models. Many of the proposed immunological mechanisms leading to primary hypertension are paralleled in autoimmune rheumatic disorders. Read More

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http://doi.wiley.com/10.1111/bph.14604
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http://dx.doi.org/10.1111/bph.14604DOI Listing
February 2019
3 Reads

A novel cyclic biased agonist of the apelin receptor, MM07, is disease modifying in the rat monocrotaline model of pulmonary arterial hypertension.

Br J Pharmacol 2019 Feb 2. Epub 2019 Feb 2.

Experimental Medicine and Immunotherapeutics, University of Cambridge, Level 6, Centre for Clinical Investigation, Box 110, Addenbrooke's Hospital, Cambridge, CB2 0QQ, UK.

Background And Purpose: Apelin is an endogenous vasodilatory and inotropic peptide that is down-regulated in human pulmonary arterial hypertension, however, the density of the apelin receptor is not significantly attenuated. We hypothesised that a G protein-biased apelin analogue MM07, which is more stable than the endogenous apelin peptide, may be beneficial in this condition with the advantage of reduced β-arrestin mediated receptor internalisation with chronic use.

Experimental Approach: Male Sprague-Dawley rats received either monocrotaline to induce pulmonary arterial hypertension or saline and then daily intraperitoneal injections of either MM07 or saline for 21 days. Read More

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http://doi.wiley.com/10.1111/bph.14603
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http://dx.doi.org/10.1111/bph.14603DOI Listing
February 2019
3 Reads
4.842 Impact Factor

The delta opioid receptor positive allosteric modulator BMS 986187 is a G protein biased allosteric agonist.

Br J Pharmacol 2019 Feb 2. Epub 2019 Feb 2.

Department of Pharmacology and Edward F. Domino Research Center, University of Michigan Medical School, Ann Arbor, Michigan.

Background And Purpose: The delta opioid receptor (DOPr) is an emerging target for the management of chronic pain and depression. Studies have highlighted the potential of biased signaling, the preferential activation of one signaling pathway over another downstream of DOPr, to generate a better therapeutic profile. BMS 986187 is a recently discovered positive allosteric modulator (PAM) of the DOPr. Read More

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http://dx.doi.org/10.1111/bph.14602DOI Listing
February 2019

Potent effects of dioscin against hepatocellular carcinoma through regulating TIGAR-mediated apoptosis, autophagy and DNA damage.

Br J Pharmacol 2019 Feb 2. Epub 2019 Feb 2.

College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian, 116044, China.

Background And Purpose: Dioscin shows potent effects against cancers. It is necessary to deeply investigate the pharmacological activities and mechanisms of disocin on hepatocellular carcinoma (HCC).

Experimental Approach: The models on SMMC7721 and HepG2 cells, DEN-induced primary liver cancer in rats, and cell xenografts in nude mice were used. Read More

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http://dx.doi.org/10.1111/bph.14594DOI Listing
February 2019
2 Reads

Sex differences in mouse models of fear inhibition: fear extinction, safety learning, and fear - safety discrimination.

Br J Pharmacol 2019 Feb 2. Epub 2019 Feb 2.

Department of Pharmacology and Therapeutics, School of Biomedical Sciences, University of Melbourne, Parkville, VIC, 3052, Australia.

Background And Purpose: Women are overrepresented in Posttraumatic stress disorder (PTSD); a mental disorder characterised by ineffective inhibition of fear. The use of male animals dominates pre-clinical studies, which may contribute to a lack of understanding as to why this disparity exists. Thus, the current study explores sex differences in three mouse models of fear inhibition. Read More

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http://dx.doi.org/10.1111/bph.14600DOI Listing
February 2019
2 Reads

Targeting amyloid clearance in Alzheimer's disease as a therapeutic strategy.

Br J Pharmacol 2019 Feb 2. Epub 2019 Feb 2.

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

Targeting the amyloid (Aβ) peptide cascade has been at the heart of therapeutic developments in Alzheimer disease research for more than 25 years yet no successful drugs have reached the marketplace based on this hypothesis. Nevertheless, the genetic and other evidence remains strong, if not overwhelming, that Aβ is central to the disease process. Most attention has focused on the biosynthesis of Aβ from its precursor protein APP through the successive actions of the β- and γ-secretases leading to the development of inhibitors of these membrane proteases. Read More

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http://dx.doi.org/10.1111/bph.14593DOI Listing
February 2019
1 Read

TMEM16A is Implicated in the Regulation of Coronary Flow and is Altered in Hypertension.

Br J Pharmacol 2019 Feb 2. Epub 2019 Feb 2.

Vascular Biology Research Centre, Institute of Molecular and Clinical Sciences, St George's University of London, London, SW17 0RE, UK.

Background And Purpose: Coronary artery disease leads to ischaemic heart disease and ultimately myocardial infarction. Thus is it important to determine the factors that regulate coronary blood flow. Ca -activated chloride channels contribute to the regulation of arterial tone; however, their role in coronary arteries is unknown. Read More

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http://doi.wiley.com/10.1111/bph.14598
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http://dx.doi.org/10.1111/bph.14598DOI Listing
February 2019
3 Reads

Opposite effects of cannabinoid CB1 and CB2 receptors on antipsychotic clozapine-induced cardiotoxicity.

Br J Pharmacol 2019 Feb 1. Epub 2019 Feb 1.

Department of Forensic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China.

Background And Purpose: Clozapine is an atypical antipsychotic drug that is very efficacious in treating psychosis but the risk of severe cardiotoxicity limits its clinical use. The present study investigated the myocardial injury effects of clozapine and assessed the involvement of cannabinoid receptors in clozapine cardiotoxicity.

Experimental Approach: The clozapine alone or in combination with selective cannabinoid receptor antagonists or agonists were used to treat mice and cardiomyocytes. Read More

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http://dx.doi.org/10.1111/bph.14591DOI Listing
February 2019

Targeting the phosphorylation site of MARCKS alleviates symptoms of steroid-resistant like asthma in a murine model.

Br J Pharmacol 2019 Feb 1. Epub 2019 Feb 1.

Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taiwan.

Background: Myristoylated alanine-rich C kinase substrate (MARCKS), a protein kinase C (PKC) substrate, facilitates mucus production and neutrophil migration. However, the effects of therapeutic procedures targeting the phosphorylation site of MARCKS on steroid-resistant asthma and the mechanisms underlying such effects have not yet been investigated. We designed a peptide that targets the MARCKS phosphorylation site (MPS peptide) and assessed its therapeutic potential against steroid-resistant asthma. Read More

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http://dx.doi.org/10.1111/bph.14596DOI Listing
February 2019

Blockage of sphingosine-1-phosphate receptor 2 (S1P ) attenuates allergic asthma in mice.

Br J Pharmacol 2019 Feb 1. Epub 2019 Feb 1.

Molecular Inflammation Research Center for Aging Intervention (MRCA) and College of Pharmacy, Pusan National University, Busan, 46241, Republic of Korea.

Background: S1P receptors have been implicated in degranulation of mast cells. However, functions of S1P have not been investigated in an in vivo model of allergic asthma.

Methods: Using an ovalbumin (OVA)-induced asthma model, function of S1P was evaluated in S1P -deficient mice or in mice treated with JTE-013, a selective antagonist of S1P . Read More

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http://dx.doi.org/10.1111/bph.14597DOI Listing
February 2019
1 Read

Loganetin protects against rhabdomyolysis-induced acute kidney injury by modulating the Toll-like receptor 4 signaling pathway.

Br J Pharmacol 2019 Jan 31. Epub 2019 Jan 31.

Shandong New Time Pharmaceutical Co., LTD., Lunan Pharmaceutical Group Co., Ltd., Linyi, China.

Background And Purpose: Acute kidney injury (AKI) is a rapid renal dysfunctional disease, for which no effective drugs or therapies are available to improve prognosis. Loganetin is a natural product with unknown bioactivities. Here we identified a new protective effect and mechanism of Loganetin in rhabdomyolysis-induced AKI mice model. Read More

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http://dx.doi.org/10.1111/bph.14595DOI Listing
January 2019
4.842 Impact Factor

Aspirin eugenol ester attenuates oxidative injury of vascular endothelial cells by regulating NOS and Nrf signaling pathways.

Br J Pharmacol 2019 Feb 1. Epub 2019 Feb 1.

Key Lab of New Animal Drug Project of Gansu Province, Key Lab of Veterinary Pharmaceutical Development of Ministry of Agriculture, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou, 730050, China.

Background And Purpose: Aspirin eugenol ester (AEE) is a new drug compound synthesized by combining aspirin with eugenol. It was reported to possess anti-thrombotic, anti-atherosclerotic and anti-oxidative effects. However, its molecular mechanism against oxidative injury is unclear. Read More

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http://dx.doi.org/10.1111/bph.14592DOI Listing
February 2019

Pharmacological impact of antiretroviral therapy on platelet function to investigate HIV-associated cardiovascular risk.

Br J Pharmacol 2019 Jan 25. Epub 2019 Jan 25.

National Heart and Lung Institute, Imperial College London, London, UK.

Background And Purpose: Some clinical studies have reported increased myocardial infarction in people living with HIV taking the antiretroviral abacavir sulphate (ABC). Given that clinical studies contain confounding variables (e.g. Read More

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http://doi.wiley.com/10.1111/bph.14589
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http://dx.doi.org/10.1111/bph.14589DOI Listing
January 2019
3 Reads

Highlighted mechanistic aspects in the chemical biology of reactive sulfur species.

Br J Pharmacol 2019 Feb;176(4):511-513

Botanical Institute, Cluster of Excellence on Plant Sciences (CEPLAS), University of Cologne, Cologne, Germany.

Linked Articles: This article is part of a themed section on Chemical Biology of Reactive Sulfur Species. 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.14551DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6346067PMC
February 2019

Mitochondrial dysfunction in Alzheimer's disease: Role in pathogenesis and novel therapeutic opportunities.

Br J Pharmacol 2019 Jan 24. Epub 2019 Jan 24.

University of Kansas Alzheimer's Disease Center, Fairway, KS, 66160, USA.

Cell bioenergetic dysfunction is a common feature in neurodegenerative diseases, the most common of which is Alzheimer's disease (AD). Disrupted energy utilization implicates mitochondria at its nexus. This review summarizes some of the evidence that points to faulty mitochondrial function in AD and highlights past and current therapeutic development efforts. Read More

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http://dx.doi.org/10.1111/bph.14585DOI Listing
January 2019

LIPID MEDIATORS IN IMMUNE REGULATION AND RESOLUTION.

Br J Pharmacol 2019 Jan 23. Epub 2019 Jan 23.

Comparative Biological Sciences, Royal Veterinary College, University of London, Royal College Street, London, NW1 0TU, UK.

We are all too familiar with the events that follow a bee sting - heat, redness, swelling and pain. These are Celsus' four cardinal signs of inflammation that are driven by very well defined signals and hormones; in fact targeting the factors that drive this onset phase is the basis upon which most current anti-inflammatory therapies were developed. We are also very well aware that within a few hours these cardinal signs normally disappear. Read More

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http://dx.doi.org/10.1111/bph.14587DOI Listing
January 2019

Neutralization of interleukin-17 rescues amyloid-β-induced neuroinflammation and memory impairment.

Br J Pharmacol 2019 Jan 23. Epub 2019 Jan 23.

Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Via Domenico Montesano 49, 80131, Naples, Italy.

Background And Purpose: Alzheimer's disease (AD) is a common neurodegenerative disease characterized by a neuroinflammatory state and to date, there is no cure and its treatment represents a large unmet clinical need. The involvement of T helper 17 cells in the pathogenesis of AD-related neuroinflammation has been reported in several studies, however the role of the main cytokine, IL-17, has not been well addressed. Herein, we investigate the effects of IL-17 neutralizing antibody (IL-17Ab) injected by intracerebroventricular (ICV) or intranasal (IN) routes on amyloid-β-induced neuroinflammation and memory impairment in mice. Read More

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http://doi.wiley.com/10.1111/bph.14586
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http://dx.doi.org/10.1111/bph.14586DOI Listing
January 2019
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Sex differences in schizophrenia, bipolar disorder and PTSD: Are gonadal hormones the link?

Br J Pharmacol 2019 Jan 18. Epub 2019 Jan 18.

School of Psychological Sciences, The University of Melbourne, Parkville, VIC, Australia.

In this review, we describe the sex differences in prevalence, onset, symptom profiles and disease outcome that are evident in schizophrenia, bipolar disorder and post-traumatic stress disorder. Women with schizophrenia tend to exhibit less disease impairment than men; by contrast, women with post-traumatic stress disorder are more affected than men. The most likely candidates to explain these sex differences are gonadal hormones. Read More

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http://dx.doi.org/10.1111/bph.14584DOI Listing
January 2019
2 Reads

1,2,3,4,6 penta-O-galloyl-β-D-glucose modulates perivascular inflammation and prevents vascular dysfunction in angiotensin II-induced hypertension.

Br J Pharmacol 2019 Jan 18. Epub 2019 Jan 18.

Department of Internal and Agricultural Medicine, Jagiellonian University Medical College, Krakow, Poland.

Background And Purpose: Hypertension is a multifactorial disease, manifested by vascular dysfunction, increased superoxide production and perivascular inflammation. In this study, we have hypothesized that 1,2,3,4,6 Penta-O-Galloyl-β-D-Glucose (PGG) would inhibit vascular inflammation and protect from vascular dysfunction in an experimental model of hypertension.

Experimental Approach: PGG was administered every two days in a dose of 10 mg·kg i. Read More

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http://dx.doi.org/10.1111/bph.14583DOI Listing
January 2019
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A short perspective on the long road to effective treatments for Alzheimer's disease.

Authors:
David S Reynolds

Br J Pharmacol 2019 Jan 18. Epub 2019 Jan 18.

Alzheimer's Research UK, Riverside 3, Granta Park, Great Abington, Cambridge, CB21 6AD, United Kingdom.

Globally there are approximately 47 million people living with dementia and about two-thirds of those have Alzheimer's disease (AD). Age is the single biggest risk factor for the vast majority of sporadic AD cases and because the world's population is aging, the number of people living with AD is set to rise dramatically over the coming decades. There are currently no disease-modifying treatments for AD and the few symptomatic agents available have limited impact on the disease. Read More

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http://dx.doi.org/10.1111/bph.14581DOI Listing
January 2019
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Signaling by hydrogen sulfide and polysulfides via protein S-sulfuration.

Authors:
Hideo Kimura

Br J Pharmacol 2019 Jan 18. Epub 2019 Jan 18.

National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo, 187-8502, Japan.

Hydrogen sulfide (H S) is a signaling molecule to regulate the neuronal transmission, vascular tone, cytoprotection, inflammatory responses, angiogenesis, and oxygen sensing. Some of these functions have recently been ascribed to its oxidized form polysulfides (H S ) which can be produced by 3-mercaptopyruvate sulfurtransferase (3MST), also known as a H S producing enzyme. H S activate ion channels, tumor suppressors, transcription factors, and protein kinases. Read More

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http://dx.doi.org/10.1111/bph.14579DOI Listing
January 2019
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Spinal α -adrenoceptors and neuropathic pain modulation; therapeutic target.

Br J Pharmacol 2019 Jan 18. Epub 2019 Jan 18.

Neuroscience Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.

Neuropathic pain can arise from disease or damage to the nervous system. The most common symptoms of neuropathic pain include spontaneous pain, allodynia, and hyperalgesia. There is still limited knowledge about the factors that initiate and maintain neuropathic pain. Read More

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http://doi.wiley.com/10.1111/bph.14580
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http://dx.doi.org/10.1111/bph.14580DOI Listing
January 2019
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The BACE inhibitor NB-360 in preclinical models: From β-amyloid reduction to downstream disease-relevant effects.

Br J Pharmacol 2019 Jan 18. Epub 2019 Jan 18.

Novartis Institute for BioMedical Research, Novartis Campus, CH-4056, Basel, Switzerland.

Inhibition of Beta-site- APP Cleaving Enzyme-1 (BACE-1) is a current approach to fight the β-amyloid (Aβ) deposition in the brains of patients with Alzheimer's disease, and a number of BACE-1 inhibitors are currently being tested in clinical trials. The BACE-1 inhibitor NB-360, although not a clinical compound, turned out as a valuable pharmacological tool to investigate the effects of BACE-1 inhibition on the deposition of different Aβ species in APP transgenic mice. Furthermore, chronic animal studies with NB-360 discovered relationships between BACE-1 inhibition, Aβ deposition, and Aβ-related downstream effects on neuroinflammation, neuronal function and markers of neurodegeneration. Read More

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http://dx.doi.org/10.1111/bph.14582DOI Listing
January 2019
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Treasure Troves of Pharmacological Tools to Study TRPC1/4/5 Channels.

Authors:
Hussein N Rubaiy

Br J Pharmacol 2019 Jan 17. Epub 2019 Jan 17.

Centre for Atherothrombosis and Metabolic Disease, Hull York Medical School, University of Hull, Hull, HU6 7RX, UK.

Canonical or classical transient receptor potential 4 and 5 proteins (TRPC4 and TRPC5) assemble as homomers or heteromerize with TRPC1 protein to form functional non-selective cationic channels with high calcium permeability. These channel complexes, TRPC1/4/5, are widely expressed in nervous and cardiovascular systems, also in other human tissues and cell types. It is debatable that TRPC1 protein is able to form a functional ion channel on its own. Read More

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http://dx.doi.org/10.1111/bph.14578DOI Listing
January 2019
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Childhood Adversity and Mechanistic Links to Hypertension Risk in Adulthood.

Br J Pharmacol 2019 Jan 17. Epub 2019 Jan 17.

CardioRenal Physiology and Medicine Section, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.

Adverse childhood experiences (ACEs), defined as traumatic events in childhood that range from various of forms of abuse to household challenges and dysfunction, have devastating consequences on adult health. Epidemiological studies in humans and animal models of early life stress (ELS) have revealed a strong association and insight into the mechanistic link between ACEs and increased CVD risks. This review focuses on the mechanistic links of ACEs in humans and ELS in mice and rats to vasoactive factors and immune mediators associated with CVD and hypertension risk, as well as sex differences in these phenomena. Read More

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http://dx.doi.org/10.1111/bph.14576DOI Listing
January 2019
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The citrus flavanone hesperetin preferentially inhibits slow-inactivating currents of an LQT3 syndrome Na channel mutation.

Br J Pharmacol 2019 Jan 16. Epub 2019 Jan 16.

Laboratory of Ion Channel Research, Department of Cellular and Molecular Medicine, KU Leuven, VIB Center for Brain & Disease Research, Leuven, Belgium.

Background And Purpose: The citrus flavanone hesperetin (HSP) has been proposed for the treatment of several human pathologies, but its cardiovascular actions remain largely unexplored. Here we evaluated HSP effects on cardiac electrical and contractile activities, on aortic contraction, on the wild type voltage-gated Na channel Na 1.5 and on a channel mutant (R1623Q) associated with lethal ventricular arrhythmias in the Long QT syndrome subtype 3 (LQT3). Read More

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http://doi.wiley.com/10.1111/bph.14577
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http://dx.doi.org/10.1111/bph.14577DOI Listing
January 2019
4 Reads