Read by QxMD icon Read

British Journal of Pharmacology

Gustavo Provensi, Maria Beatrice Passani, Alessia Costa, Ivan Izquierdo, Patrizio Blandina
In this review, we describe the experimental paradigms used in preclinical studies to unravel the histaminergic brain circuits that modulate the formation and retrieval of memories associated with aversive events. Emotionally arousing events, especially bad ones, are remembered more accurately, clearly and for longer periods of time than neutral ones. Maladaptive elaborations of these memories may eventually constitute the basis of psychiatric disorders such as generalized anxiety, obsessive-compulsive disorders, post-traumatic stress disorder...
August 15, 2018: British Journal of Pharmacology
Emily Langron, Stella Prins, Paola Vergani
BACKGROUND AND PURPOSE: Cystic fibrosis (CF) is a debilitating hereditary disease caused by mutations in the CFTR gene, which encodes an anion channel. WT-CFTR gating is a non-equilibrium process. After ATP binding, CFTR enters a stable open state (O1 ). ATP hydrolysis leads it to a short-lived post-hydrolytic open state (O2 ), from which channels close. Here we use mutations to probe the mechanism of VX-770, the first compound directly targeting the CFTR protein approved for treatment of CF...
August 14, 2018: British Journal of Pharmacology
Pedro H Gobira, Ana C Oliveira, Julia S Gomes, Vivian T da Silveira, Laila Asth, Juliana R Bastos, Edleusa M Batista, Ana C Issy, Bright N Okine, Antonio C de Oliveira, Fabiola M Ribeiro, Elaine A Del Bel, Daniele C Aguiar, David P Finn, Fabricio A Moreira
BACKGROUND AND PURPOSE: The endocannabinoids anandamide and 2-arachidonoylglycerol (2-AG) bind to CB1 and CB2 receptors in the brain and modulate the mesolimbic dopaminergic pathway. This neurocircuitry is engaged by psychostimulant drugs, including cocaine. Although it is known that CB1 antagonism as well as CB2 activation inhibit certain effects of cocaine, they have been investigated separately. Here we tested the hypothesis that there is a reciprocal interaction between CB1 blockade and CB2 activation in modulating behavioural responses to cocaine...
August 12, 2018: British Journal of Pharmacology
Ketul R Chaudhary, Yupu Deng, Colin M Suen, Mohamad Taha, Thomas H Petersen, Shirley H J Mei, Duncan J Stewart
BACKGROUND AND PURPOSE: Pulmonary arterial hypertension (PAH) is a life-threatening disease that leads to progressive pulmonary hypertension, right heart failure and death. Parenteral prostaglandins, including treprostinil, a prostacyclin analogue, represent the most effective medical treatment for severe PAH. We investigated the effect of treprostinil on established severe PAH and underlying mechanisms using the rat SU5416 (SU, a vascular endothelial growth factor receptor-2 inhibitor)-chronic hypoxia (Hx) model of PAH...
August 11, 2018: British Journal of Pharmacology
Ben J Gu, James S Wiley
The P2X7 receptor (P2X7 or P2X7R) has been widely studied for ATP-induced proinflammation, but in the absence of ligand, P2X7 has a second function as a scavenger receptor which is active in the development of human brain. The scavenger activity of P2X7 is only evident in the absence of serum but is fully active in cerebrospinal fluid. P2X7 on the cell surface is present as a membrane complex and an attachment to nonmuscle myosin of the cytoskeleton is required for particle engulfment. Selective antagonists of P2X7 proinflammatory function have little effect on phagocytosis but coinheritance of a haplotype spanning in P2RX7 and P2RX4 genes has been associated with loss of P2X7 mediated phagocytosis...
August 10, 2018: British Journal of Pharmacology
Ying Cao, Shujun Chen, Yemei Liang, Ting Wu, Jianxin Pang, Shuwen Liu, Pingzheng Zhou
BACKGROUND AND PURPOSE: Carvedilol is a clinically broadly used and effective beta-blocker for treatment of congestive heart failure (CHF) and several clinical trials have demonstrated that carvedilol shows a favourable effect compared to other beta-blocking agents in patients with CHF. The mechanism underlying the advantage of carvedilol over other beta-blocking agents is not clearly understood. In addition to beta-blockers, inhibitors of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, which play a critical role in spontaneous rhythmic activity in the heart, have also been proposed to be suitable in reducing the heart rate and therefore beneficial for treatment of CHF...
August 10, 2018: British Journal of Pharmacology
I A Clark, B Vissel
While cytokines such as tumour necrosis factor (TNF) are long recognised as essential to normal cerebral physiology, the implications of their chronic excessive production within the brain are now also increasingly appreciated. Syndromes as diverse malaria and lead poisoning, as well as the non-infectious neurodegenerative diseases illustrate this. These cytokines also orchestrate changes in tau, α-synuclein, β-amyloid levels and degree of insulin resistance in most neurodegenerative states. New data on the effects of salbutamol, an anti-TNF agent, on α-synuclein and Parkinson's disease, APOE4 and tau add considerably to the rationale of the anti-TNF approach to understanding, and treating, these diseases...
August 10, 2018: British Journal of Pharmacology
Denise C Cornelius, Jesse Cottrell, Lorena M Amaral, Babbette LaMarca
Preeclampsia (PE) is a hypertensive disorder that occurs after 20 weeks of gestation, implicating the placenta as a key offender. PE is associated with an imbalance among B lymphocytes, CD4+ T lymphocytes, natural killer (NK) cells, and increased inflammatory cytokines. During early on-set preeclampsia, trophoblast invasion and placentation are impaired, leading to reduced blood flow to the fetus. In all spectrums of this disorder, a shift toward a pro-inflammatory state where regulatory cells and cytokines are decreased occurs...
August 10, 2018: British Journal of Pharmacology
Rou-Ling Cho, Chien-Chung Yang, Hui-Ching Tseng, Li-Der Hsiao, Chih-Chung Lin, Chuen-Mao Yang
BACKGROUND AND PURPOSE: Heme oxygenase-1 (HO-1) is induced by thiazolidinediones including rosiglitazone and exerts anti-inflammatory effects in various models. However, the molecular mechanisms underlying rosiglitazone-induced HO-1 expression remain largely unknown in human pulmonary alveolar epithelial cells (HPAEpiCs). EXPERIMENTAL APPROACH: HO-1 expression was determined by real time-PCR, western blotting, and promoter reporter analyses. The signaling components were investigated by using pharmacological inhibitors or specific siRNAs...
August 8, 2018: British Journal of Pharmacology
Joshua B Kohl, Anna-Theresa Mellis, Guenter Schwarz
Cysteine is one of the two key sulfur-containing amino acids with important functions in, redox homeostasis, protein functionality and metabolism. Cysteine is taken up by mammals via the diet, and can also be derived from methionine via the transsulfuration pathway. The cellular concentration of cysteine is kept within a narrow range by controlling its synthesis and degradation. There are two pathways for the catabolism of cysteine leading to sulfate, taurine and thiosulfate as terminal products. The oxidative pathway produces taurine and sulfate, while the H2 S pathway involves different enzymatic reactions leading to the formation and clearance of H2 S, an important signalling molecule in mammals, resulting in thiosulfate and sulfate...
August 8, 2018: British Journal of Pharmacology
Joseph Pierre Aboumsallem, Mudit Mishra, Ruhul Amin, Ilayaraja Muthuramu, Herman Kempen, Bart De Geest
BACKGROUND AND PURPOSE: Pleiotropic properties of high-density lipoproteins (HDL) may exert beneficial effects on the myocardium. The effect of recombinant HDLMilano on established heart failure was evaluated in C57BL/6 mice. EXPERIMENTAL APPROACH: Transverse aortic constriction (TAC) or sham operation was performed at the age of 14 weeks. Eight weeks later, TAC and sham mice were each randomised into three different groups. Reference groups were sacrificed at day 56 after operation for baseline analysis...
August 5, 2018: British Journal of Pharmacology
Clément Verkest, Emilie Piquet, Sylvie Diochot, Mélodie Dauvois, Michel Lanteri-Minet, Eric Lingueglia, Anne Baron
BACKGROUND AND PURPOSE: Acid-Sensing Ion Channels (ASICs) are neuronal proton sensors emerging as potential therapeutic targets in pain of the orofacial region. Amiloride, a non-specific ASIC blocker, has been shown to exert beneficial effects in animal models of migraine and in patients. We explored the involvement of the ASIC1-subtype in cutaneous allodynia, a hallmark of migraine affecting cephalic and extra-cephalic regions in about 70% of migrainers. EXPERIMENTAL APPROACH: We investigated the effects on cephalic and extra-cephalic mechanical sensitivity of systemic injections of amiloride and mambalgin-1, a specific inhibitor of ASIC1a- and ASIC1b-containing channels, in a rodent model of acute and chronic migraine induced by intraperitoneal injections of isosorbide dinitrate...
August 5, 2018: British Journal of Pharmacology
Chao Chen, Biao Xu, Xuerui Shi, Mengna Zhang, Qinqin Zhang, Ting Zhang, Weidong Zhao, Run Zhang, Zilong Wang, Li Ning, Quan Fang
BACKGROUND AND PURPOSE: The voltage-gated sodium channel NaV 1.7 is considered a therapeutic target for pain treatment based on human genetic evidence. GpTx-1 and its potent analog [Ala5 , Phe6 , Leu26 , Arg28 ]GpTx-1 (GpTx-1-71) were recently characterized as NaV 1.7 inhibitors in vitro. Furthermore, the present work was conducted to investigate the analgesic properties of these two peptides in different pain models after spinal administration. EXPERIMENTAL APPROACH: The antinociceptive activities of both GpTx-1 and GpTx-1-71 were investigated in mouse models of acute, visceral, inflammatory and neuropathic pain...
August 4, 2018: British Journal of Pharmacology
Chaonan Ye, Kun Han, Jinxiu Lei, Kui Zeng, Su Zeng, Haixing Ju, Lushan Yu
BACKGROUND AND PURPOSE: CNT2 is a transporter that mediates the uptake of both natural nucleosides and nucleoside-derived drugs. Therefore, it is important both physiologically and pharmacologically. However, CNT2 expression is significantly repressed in colorectal cancer (CRC). The aim of this study was to elucidate the mechanism underlying CNT2 repression in CRC. EXPERIMENTAL APPROACH: The repression of CNT2 in CRC was identified using Western blot and RT-qPCR...
August 4, 2018: British Journal of Pharmacology
Liliana Raimundo, Margarida Espadinha, Joana Soares, Joana B Loureiro, Marco G Alves, Maria M M Santos, Lucília Saraiva
BACKGROUND AND PURPOSE: The impairment of the tumour suppressor p53 pathway is a major event in human cancer. This makes p53 activation one of the most appealing therapeutic strategies to halt cancer. Herein, we identified a new selective p53 activator, and investigated its potential as an anticancer agent. EXPERIMENTAL APPROACH: The anti-proliferative activity of (R)-tryptophanol-derived bicyclic lactam SYNAP was evaluated in an array of human cancer cells with different p53 status...
August 4, 2018: British Journal of Pharmacology
Fabio Arturo Iannotti, Ester Pagano, Aniello Schiano Moriello, Filomena Grazia Alvino, Nicolina Cristina Sorrentino, Luca D'Orsi, Elisabetta Gazzerro, Raffaele Capasso, Elvira De Leonibus, Luciano De Petrocellis, Vincenzo Di Marzo
BACKGROUND AND PURPOSE: Duchenne muscular dystrophy (DMD), caused by dystrophin deficiency, results in chronic inflammation and irreversible skeletal muscle degeneration. Moreover, the associated impairment of autophagy leads to the accumulation of damaged intracellular organelles that greatly contribute to the aggravation of muscle damage. We explored the possibility of using non-euphoric compounds present in Cannabis sativa, including cannabidiol (CBD), cannabidivarin (CBDV) and tetrahydrocannabidivarin (THCV) to reduce inflammation, restore functional autophagy and positively enhance muscle function in vivo...
August 3, 2018: British Journal of Pharmacology
Kenton M Sanders, Sean M Ward
Nitric oxide (NO) is a neurotransmitter released from enteric inhibitory neurons and responsible for modulating gastrointestinal (GI) motor behaviors. Enteric neurons express NOS1 that associates with membranes of nerve varicosities. NO released from neurons binds to soluble guanylate cyclase (sGC) in post-junctional cells to generate cGMP. cGMP-dependent protein kinase type 1 (PRKG1) is a major mediator of effects, but perhaps not the only pathway involved in cGMP-mediated effects in GI muscles based on gene deletion studies...
July 31, 2018: British Journal of Pharmacology
Sofya Pozdniakova, Mariona Guitart-Mampel, Gloria Garrabou, Giulietta Di Benedetto, Yury Ladilov, Vera Regitz-Zagrosek
BACKGROUND AND PURPOSE: Mitochondria possess their own source of cAMP, i.e., soluble adenylyl cyclase (sAC). Activation or expression of the mitochondrial sAC promotes mitochondrial function. Estrogen receptor signaling plays an essential role in the regulation of mitochondrial function. We aimed to determine whether 17β-estradiol may affect mitochondrial cAMP signaling. EXPERIMENTAL APPROACH: The expression of the intra-mitochondrial proteins (western blot), mitochondrial cAMP content (FRET-based live imaging and mass spectrometry assay), mitochondrial membrane potential and COX activity were analyzed in H9C2 and C2C12 cells...
July 26, 2018: British Journal of Pharmacology
Ivan Weinsanto, Alexis Laux-Biehlmann, Jinane Mouheiche, Tando Maduna, François Delalande, Virginie Chavant, Florian Gabel, Pascal Darbon, Alexandre Charlet, Pierrick Poisbeau, Marc Lamshöft, Alain Van Dorsselaer, Sarah Cianferani, Marie-Odile Parat, Yannick Goumon
BACKGROUND AND PURPOSE: Chronic administration of medication can have an important impact on metabolic enzymes leading to physiological adaptations. Morphine metabolism in the liver has been extensively studied following acute morphine treatment but morphine metabolic processes in the central nervous system are poorly characterised. Long-term morphine treatment is limited by the development of tolerance, resulting in a decrease of its analgesic effect. Whether or not morphine analgesic tolerance affects in vivo brain morphine metabolism and blood-brain barrier (BBB) permeability remains a major pending question...
July 26, 2018: British Journal of Pharmacology
Martin A Sticht, David D Lau, Catherine M Keenan, Jean-Baptiste Cavin, Maria Morena, Venkata Kiran Vemuri, Alexandros Makriyannis, Benjamin F Cravatt, Keith A Sharkey, Matthew N Hill
BACKGROUND AND PURPOSE: Stress is known to reduce food intake. Many aspects of the stress response and feeding are regulated by the endocannabinoid (eCB) system, but the roles of anandamide (AEA) and 2-arachidonoyl glycerol (2-AG) in stress-induced anorexia are unclear. EXPERIMENTAL APPROACH: Effects of acute restraint stress on eCBs were investigated in male Sprague Dawley rats. Systemic and central pharmacological inhibition of fatty acid amide hydrolase (FAAH) or monoacylglycerol lipase (MAGL) was used to determine the potential of elevated AEA and 2-AG to stimulate homeostatic feeding and modulate food consumption after stress...
July 26, 2018: British Journal of Pharmacology
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"