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British Journal of Pharmacology

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https://www.readbyqxmd.com/read/29451703/mechanisms-of-imidazoline-i-2-receptor-agonist-induced-antinociception-in-rats-involvement-of-monoaminergic-neurotransmission
#1
Justin N Siemian, Kaixuan Wang, Yanan Zhang, Jun-Xu Li
BACKGROUND AND PURPOSE: Although studies have established the antinociceptive efficacies of imidazoline I 2 receptor (I 2 R) agonists, its exact post-receptor mechanism remains unknown. This study tested the hypothesis that monoaminergic transmission is critical for I 2 R agonist-induced antinociception. EXPERIMENTAL APPROACH: The von Frey filament test was used to examine the antinociceptive effects of the I 2 R agonists 2-BFI and CR4056 on chronic constriction injury (CCI)-induced neuropathic pain or complete Freund's adjuvant (CFA)-induced inflammatory pain in rats...
February 16, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29451687/gpcrs-in-context-sexual-dimorphism-in-the-cardiovascular-system
#2
REVIEW
Margaret A Mouat, James L J Coleman, Nicola J Smith
Cardiovascular disease remains the largest cause of mortality worldwide and there is a clear gender gap in disease occurrence: men are predisposed to earlier onset of cardiovascular disease, including atherosclerosis and hypertension, than are women. Oestrogen may be a driving factor for female-specific cardioprotection, though androgens and sex chromosomes are also likely to contribute to sexual dimorphism in the cardiovascular system. Many G protein-coupled receptor (GPCR)-mediated processes are involved in cardiovascular homeostasis and some exhibit clear sex-divergence...
February 16, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29447434/alterations-in-melatonin-and-serotonin-signalling-in-the-colonic-mucosa-of-mice-with-dextran-sodium-sulfate-induced-colitis
#3
Sarah J MacEachern, Catherine M Keenan, Evangelia Papakonstantinou, Keith A Sharkey, Bhavik Anil Patel
BACKGROUND AND PURPOSE: Inflammatory bowel disease (IBD) is characterized by pain, bleeding, cramping and altered gastrointestinal (GI) function. Changes in mucosal serotonin (5-HT) signalling occur in animal models of colitis and in humans suffering from IBD. Melatonin is co-released with 5-HT from the mucosa and has a wide variety of actions in the GI tract. Here we examined how melatonin signalling is affected by colitis and determined how this relates to 5-HT signalling. EXPERIMENTAL APPROACH: Using electroanalytical approaches, we investigated how 5-HT release, reuptake and availability as well as melatonin availability are altered in dextran sodium sulfate (DSS)-induced colitis in mice...
February 15, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29447430/aucubin-protects-against-pressure-overload-induced-cardiac-remodelling-via-%C3%AE-3-ar-nnos-cascades
#4
Qing-Qing Wu, Yang- Xiao, Ming-Xia Duan, Yuan Yuan, Xiao-Han Jiang, Zheng Yang, Hai-Han Liao, Wei Deng, Qi-Zhu Tang
BACKGROUND AND PURPOSE: Aucubin, the predominant component of Eucommia ulmoides Oliv., plays an indispensable role in regulating oxidative stress. Considering that oxidative stress has previously been demonstrated to contribute to acute and chronic myocardial injury, we tested the effects of aucubin on cardiac remodelling and heart failure. EXPERIMENTAL APPROACH: In the first set of experiments, H9c2 cardiomyocytes and neonatal rat cardiomyocytes pre-treated with aucubin (1, 3 10, 25, 50 μM) were challenged with phenylephrine...
February 15, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29446826/1-3-6-7-tetrahydroxy-8-prenylxanthone-ameliorates-inflammatory-responses-resulted-in-by-the-paracrine-interaction-of-adipocytes-and-macrophages
#5
Dan Li, Qianyu Liu, Wen Sun, Xiuping Chen, Ying Wang, Yuxiang Sun, Ligen Lin
BACKGROUND AND PURPOSE: Chronic inflammation in adipose tissue is critical in the onset and development of insulin resistance and type 2 diabetes. Macrophage infiltration into adipose tissue and pro-inflammatory polarization play key roles in adipose tissue inflammation. The fruit hull of mangosteen (Garcinia mangostana) has been used in traditional medicine for treatment of various inflammatory diseases. However, its role in regulating adipose tissue inflammation is unexplored. This study was designed to identify xanthones from G...
February 15, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29406581/crf2-receptor-deficiency-eliminates-social-behaviour-deficits-and-vulnerability-induced-by-cocaine
#6
Nadège Morisot, Romain Monier, Catherine Le Moine, Mark J Millan, Angelo Contarino
BACKGROUND AND PURPOSE: Poor social behaviour and vulnerability to stress are major clinical features of stimulant use disorders. The corticotropin-releasing factor (CRF) system mediates stress responses and might underlie substance use disorders; however, its implication in social impairment induced by stimulant substances remains unknown. CRF signalling is mediated by two receptor types, CRF1 and CRF2 . The present study investigated the role for the CRF2 receptor in social behaviour deficits, vulnerability to stress and related brain alterations induced by cocaine administration and withdrawal...
February 6, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29405261/dual-oxidase-a-novel-therapeutic-target-in-allergic-disease
#7
REVIEW
Albert van der Vliet, Karamatullah Danyal, David E Heppner
NADPH oxidases represent a family of enzymes that mediate regulated cellular production of reactive oxygen species (ROS), and play various functional roles in physiology. Among the NOX family, the dual oxidases DUOX1 and DUOX2 are prominently expressed in epithelial cell types at mucosal surfaces, and have therefore been considered to have important roles in innate host defense pathways. Recent studies have shed important insights into the host defense mechanisms of DUOX enzymes, which control innate immune response pathways in response to either microbial or allergic triggers...
February 5, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29394501/functional-interplay-between-lxr-and-ampk%C3%AE-inhibits-atherosclerosis-in-apoe-deficient-mice-a-new-anti-atherogenic-strategy
#8
Chuanrui Ma, Wenwen Zhang, Xiaoxiao Yang, Ying Liu, Lipei Liu, Ke Feng, Xiaomeng Zhang, Shu Yang, Lei Sun, Miao Yu, Jie Yang, Xiaoju Li, Wenquan Hu, Robert Q Miao, Yan Zhu, Luyuan Li, Jihong Han, Yuanli Chen, Yajun Duan
BACKGROUND AND PURPOSE: LXR agonist (T317) reduces atherosclerosis while inducing fatty liver. Metformin activates energy metabolism by activating AMPKα. In this study, we determined if the interaction between metformin and T317 can inhibit atherosclerosis without activation of hepatic lipogenesis. EXPERIMENTAL APPROACH: ApoE deficient mice were treated with T317, metformin or both contained in a high-fat diet for 16 weeks. After treatment, mouse aorta, liver, macrophage and serum samples were collected to determine atherosclerotic lesions, fatty liver, lipid profiles and expression of related molecules...
February 2, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29394499/anti-inflammatory-therapies-in-myocardial-infarction-failures-hopes-and-challenges
#9
REVIEW
Shuaibo Huang, Nikolaos G Frangogiannis
In the infarcted heart, damage-associated molecular patterns released by necrotic cells trigger both myocardial and systemic inflammatory responses. Induction of chemokines and cytokines and upregulation of endothelial adhesion molecules mediate leukocyte recruitment in the infarcted myocardium. Inflammatory cells clear the infarct from dead cells and matrix debris and activate reparative myofibroblasts and vascular cells, but may also contribute to adverse fibrotic remodeling of viable segments, accentuate cardiomyocyte apoptosis and exert arrhythmogenic actions...
February 2, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29394497/the-current-state-of-gpcr-based-drug-discovery-to-treat-metabolic-disease
#10
REVIEW
Kyle W Sloop, Paul J Emmerson, Michael A Statnick, Francis S Willard
One approach of modern drug discovery is to identify agents that enhance or diminish signal transduction cascades in various cell types and tissues by modulating the activity of G-protein coupled receptors (GPCRs). This strategy has resulted in the development of new medicines to treat many conditions, including cardiovascular disease, psychiatric disorders, HIV/AIDS, certain forms of cancer, and type 2 diabetes mellitus (T2DM). These successes justify further pursuit of GPCRs as disease targets and provide key learning that should help guide identifying future therapeutic agents...
February 2, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29361192/acute-ethanol-exposure-has-bidirectional-actions-on-the-endogenous-neuromodulator-adenosine-in-rat-hippocampus
#11
Victoria Hughes, Magnus J E Richardson, Mark J Wall
BACKGROUND AND PURPOSE: Ethanol is a widely used recreational drug with complex effects on physiological and pathological brain function. In epileptic patients the use of ethanol can modify seizure initiation and subsequent seizure activity with reports of ethanol being both pro and anti-convulsant. One proposed target of ethanol's actions is the neuromodulator adenosine, which is released during epileptic seizures to feedback and inhibit the occurrence of subsequent seizures. Here we have investigated the actions of acute ethanol exposure on adenosine signalling in rat hippocampus...
January 23, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29352769/resolvin-e1-resolvin-d1-and-resolvin-d2-inhibit-constriction-of-rat-thoracic-aorta-and-human-pulmonary-artery-induced-by-the-thromboxane-mimetic-u46619
#12
Melanie Jannaway, Christopher Torrens, Jane A Warner, Anthony P Sampson
BACKGROUND AND PURPOSE: Omega-6 fatty acid-derived lipid mediators such as prostanoids, thromboxane and leukotrienes have well-established roles in regulating both inflammation and smooth muscle contractility. Resolvins are derived from omega-3 fatty acids and have important roles in promoting the resolution of inflammation, but their activity on smooth muscle contractility is unknown. We investigated whether resolvin E1 (RvE1), resolvin D1 (RvD1) and resolvin D2 (RvD2) can modulate contractions of isolated segments of rat thoracic aorta (RTA) or human pulmonary artery (HPA) induced by the α1 -adrenoceptor agonist phenylephrine or the stable thromboxane A2 mimetic U46619...
January 20, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29352742/cambogin-suppresses-dextran-sulphate-sodium-induced-colitis-by-enhancing-treg-cell-stability-and-function
#13
Yue Lu, Na-Mi Kim, Yi-Wen Jiang, Hong Zhang, Dan Zheng, Fu-Xiang Zhu, Rui Liang, Bin Li, Hong-Xi Xu
BACKGROUND AND PURPOSE: Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory disorder of gastrointestinal tract, and the dysfunction of immune regulation plays a critical role in IBD. Reflecting the limited use of current drugs and therapies for IBD treatment, it is necessary to explore novel drugs or therapies for this disease. We investigated the effect of cambogin in a mouse model of dextran sulphate sodium (DSS)-induced colitis and whether cambogin attenuates inflammation via Treg-cell-mediated immune modulation...
January 20, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29352503/in-vivo-effects-of-%C3%AE-opioid-receptor-agonist-%C3%AE-opioid-receptor-antagonist-peptidomimetics-following-acute-and-repeated-administration
#14
Jessica P Anand, Kelsey E Kochan, Anthony F Nastase, Deanna Montgomery, Nicholas W Griggs, John R Traynor, Henry I Mosberg, Emily M Jutkiewicz
BACKGROUND AND PURPOSE: Mu opioid receptor (μ-receptor) agonists are used for pain management, but produce adverse effects including tolerance, dependence, and euphoria. The co-administration of a μ-receptor agonist with a delta opioid receptor (δ-receptor) antagonist has been shown to produce antinociception with reduced development of some side effects. We characterized the effects of three μ-receptor agonist/δ-receptor antagonist peptidomimetics in vivo after acute and repeated administration to determine if this profile provides a viable alternative to traditional opioid analgesics...
January 19, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29338087/thrombospondin-4-acts-on-pre-synaptic-calcium-channel-alpha-2-delta-1-subunit-to-induce-synaptogenesis-between-sensory-and-spinal-cord-neurons-through-a-t-type-calcium-channel-dependent-pathway-that-is-blocked-by-early-low-dose-gabapentin-treatments
#15
Yanhui Peter Yu, Nian Gong, Tae Dong Kweon, Benjamin Vo, Z David Luo
BACKGROUND AND PURPOSE: Nerve injury induces concurrent upregulation of calcium channel alpha-2-delta-1 subunit (Cav α2 δ1 ) and extracellular matrix protein thrombospondin-4 (TSP4) in dorsal root ganglia and dorsal spinal cord, leading to neuropathic pain state development. Interactions of these proteins promote aberrant excitatory synaptogenesis that contributes to neuropathic pain state development through unknown mechanisms. We investigated the contributory role of Cav α2 δ1 /TSP4 to synaptogenesis, and pathway involved in vitro, and whether gabapentin could block this process and pain development in vivo...
January 16, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29338075/lkb1-ampk-mediated-regulation-by-gentiopicroside-ameliorates-p2x7r-dependent-alcoholic-hepatosteatosis
#16
Xia Li, Yu Zhang, Quan Jin, Kai-Li Xia, Min Jiang, Ben-Wen Cui, Yan-Ling Wu, Shun-Zong Song, Li-Hua Lian, Ji-Xing Nan
BACKGROUND AND PURPOSE: Regulating P2x7R-NLRP3 inflammasome activation might be a potential therapeutic strategy to treat alcoholic hepatosteatosis. We investigated whether this process would be modulated by gentiopicroside (GPS), which is the main active secoiridoid glycoside from Gentiana manshurica Kitagawa. EXPERIMENTAL APPROACH: In vivo models of acute and chronic alcoholic hepatosteatosis were established by intragastrically administrated ethanol or using chronic plus binge ethanol feeding of Lieber-DeCarli liquid diet to male C57BL/6 mice...
January 16, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29338070/the-use-of-chemogenetics-in-behavioural-neuroscience-receptor-variants-targeting-approaches-and-caveats
#17
REVIEW
Erin J Campbell, Nathan J Marchant
The last decade has seen major advances in neuroscience tools allowing us to selectively modulate cellular pathways in freely moving animals. Chemogenetic approaches such as Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) permit the remote control of neuronal function by systemic drug administration. These approaches have dramatically advanced our understanding of the neural control of behaviour. Here we review the different techniques and genetic approaches available for the restriction of chemogenetic receptors to defined neuronal populations...
January 16, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29338068/single-and-combined-effects-of-plant-derived-thc-cbd-and-synthetic-win-55-212-cannabinoids-on-cognition-and-cannabinoid-associated-withdrawal-signs-in-mice
#18
Alyssa M Myers, Patrick B Siegele, Jeffrey D Foss, Ronald F Tuma, Sara Jane Ward
BACKGROUND AND PURPOSE: It has been suggested that the non-euphorogenic phytocannabinoid cannabidiol (CBD) can ameliorate adverse effects of delta-9-tetrahydrocannabinol (THC). We determined whether CBD ameliorates cognitive deficits and withdrawal signs induced by cannabinoid CB1/CB2 receptor agonists or produces these pharmacological effects on its own. EXPERIMENTAL APPROACH: The effects of THC or the CB1/CB2 receptor full agonist WIN55212 (WIN) alone, CBD alone, or their combination were tested across a range of doses...
January 16, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29333604/adiponectin-inhibits-inflammatory-cytokines-production-by-beclin-1-phosphorylation-and-bcl-2-mrna-destabilization-role-for-autophagy-induction
#19
Nirmala Tilija Pun, Pil-Hoon Park
BACKGROUND AND PURPOSE: Adiponectin potently suppresses inflammatory mediator production. Autophagy is known to play a critical role in modulating inflammatory responses by adiponectin. However, the underlying mechanisms are not clearly understood. Interaction between Beclin-1 and Bcl-2 is a critical event in autophagy induction. We examined the effects of globular adiponectin (gAcrp) on the Beclin-1/Bcl-2 association and its underlying mechanisms. EXPERIMENTAL APPROACH: The effect of gAcrp on the interaction between Beclin-1 and Bcl-2 was examined by immunoprecipitation followed by Western blotting...
January 14, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29329501/sustained-plasma-hepcidin-suppression-and-iron-elevation-by-anticalin-derived-hepcidin-antagonist-in-cynomolgus-monkey
#20
Andreas M Hohlbaum, Hendrik Gille, Stefan Trentmann, Maria Kolodziejczyk, Barbara Rattenstetter, Coby M Laarakkers, Galina Katzmann, Hans Jürgen Christian, Nicole Andersen, Andrea Allersdorfer, Shane A Olwill, Bernd Meibohm, Laurent P Audoly, Dorine W Swinkels, Rachel P L van Swelm
BACKGROUND AND PURPOSE: Anaemia of chronic disease (ACD) has been linked to iron restricted erythropoiesis imposed by high circulating levels of hepcidin, a 25 amino acid hepatocyte-derived peptide that controls systemic iron homeostasis. Here we report the engineering of the human lipocalin-derived, small protein-based Anticalin PRS-080 hepcidin antagonist with high affinity and selectivity. EXPERIMENTAL APPROACH: Anticalin- and hepcidin-specific pharmacokinetic/pharmacodynamic modelling was used to design and select the suitable drug candidate based on half life extension and duration of hepcidin suppression...
January 12, 2018: British Journal of Pharmacology
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