Abstract：
BACKGROUND AND PURPOSE:Adenosine A2A receptor stimulation promotes the synthesis of collagen type I and type III (Col1 and Col3), mediators of fibrosis and scarring. The A2A receptor modulates collagen balance via cAMP/PKA/p38-MAPK/Akt pathways. Wnt signalling is important in fibrosis and the cAMP and Wnt pathways converge. Because the A2A receptor is Gs-linked and increases cAMP, we determined whether A2A receptors and Wnt signalling interact. EXPERIMENTAL APPROACH:Total β-catenin, de-phosphorylated β-catenin (canonical activation, de-phospho β-catenin) and phosphorylated β-catenin at Ser552 (non-canonical activation, p-Ser552 β-catenin) levels were determined in primary human dermal fibroblasts, cytosol and nucleus, by western blot analysis and fluorescence microscopy, before and after stimulation by A2A receptor-selective agonist CGS21680, with/without A2A receptor-selective antagonist (SCH56261) pretreatment. β-Catenin was knocked down by transfection with scrambled-siRNA or specific-siRNA, and Col1 and Col3 levels determined by western blots. KEY RESULTS:CGS21680 stimulation rapidly (15 min) increased cellular β-catenin levels. Both de-phospho β-catenin and p-Ser552 β-catenin levels were also increased. CGS21680 stimulated the translocation of total de-phospho and p-Ser552 β-catenin to the nucleus. A2A receptor-stimulation increased Col1 synthesis similarly in β-catenin knockeddown and scrambled cells. However, β-catenin knockdown abolished the increase in Col3 synthesis induced in A2A receptor-stimulated fibroblasts. CONCLUSIONS AND IMPLICATIONS:A2A receptor stimulation promotes Col3 synthesis via the activation of canonical and non-canonical β-catenin, consistent with a role for A2A receptors in dermal fibrosis and scarring.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Shaikh G,Zhang J,Perez-Aso M,Mediero A,Cronstein Bdoi
10.1111/bph.13615subject
Has Abstractpub_date
2016-12-01 00:00:00pages
3279-3291issue
23eissn
0007-1188issn
1476-5381journal_volume
173pub_type
杂志文章abstract：:1. Our study was aimed at investigating the duration of the bronchodilator action of the antimuscarinc drug glycopyrrolate compared to tiotropium and ipratropium. In the guinea-pig isolated trachea, the time (t1/2) necessary for a contractile response to carbachol (0.3 microM) to return to 50% recovery after washout o...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0706724
更新日期：2006-06-01 00:00:00
abstract：:The aim of the present study was to determine whether inhibition of cyclic nucleotide phosphodiesterase (PDE) modulates the stimulated generation of the cytokines, interleukin-4 (IL-4) and IL-13, from human basophils. This was addressed by evaluating the effects of both nonselective and selective inhibitors of PDEs on...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0705892
更新日期：2004-08-01 00:00:00
abstract：:1 The appearance of pancreatic muscarinic receptors during development has been measured by use of the specific ligand [3H]-quinuclidinyl benzilate ([3H]-QNB). 2 QNB binding sites are present in foetal pancreas; their maximal concentration is attained at the age of 30 days and a significant decrease is observed in one...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1981.tb10428.x
更新日期：1981-06-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Erectile dysfunction is highly prevalent in diabetic patients and PDE V inhibitors are effective and safe for the treatment of erectile dysfunction in men with diabetes. Therefore, in this study we investigated whether a pharmacokinetic interaction occurs between DA-8159 and metformin, as both dr...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0707680
更新日期：2008-04-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Cannabidiol (CBD) has emerged as an interesting compound with therapeutic potential in several CNS disorders. However, whether it can modulate synaptic activity in the CNS remains unclear. Here, we have investigated whether CBD modulates synaptic transmission in rat hippocampal cultures and acute...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2010.01015.x
更新日期：2011-01-01 00:00:00
abstract：:The above article, published by the British Journal of Pharmacology in October 2015 (https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1111/bph.13259), has been retracted by agreement between the authors, the journal Editor in Chief and John Wiley & Sons Limited. The retraction has been agreed owing to the discovery...
journal_title：British journal of pharmacology
pub_type： 杂志文章,撤回出版物
doi：10.1111/bph.14349
更新日期：2018-07-01 00:00:00
abstract：:1 Non-adrenergic non-cholinergic (NANC) vasodilator nerves regulate tone in certain vascular beds. We have investigated the mechanisms of the NANC dilator response in the isolated small mesenteric artery of the rabbit by use of the tension myograph. 2 Small second or third order (150-300 microm in diameter) arteries o...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701610
更新日期：1998-01-01 00:00:00
abstract：:In addition to their classical known effects, such as analgesia, impairment of cognition and learning and appetite enhancement, cannabinoids have also been related to the regulation of cardiovascular responses and implicated in cardiovascular pathology. Elevated levels of endocannabinoids have been related to the extr...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0707261
更新日期：2007-06-01 00:00:00
abstract：:AMPA-type glutamate receptors are one of the most dynamic components of excitatory synapses. Their regulated addition and removal from synapses leads to long-lasting forms of synaptic plasticity, known as long-term potentiation (LTP) and long-term depression (LTD). In addition, AMPA receptors reach their synaptic targ...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1038/sj.bjp.0707525
更新日期：2008-03-01 00:00:00
abstract：:Adrenomedullin (AM) has two known receptors formed by the calcitonin receptor-like receptor (CL) and receptor activity-modifying protein (RAMP) 2 or 3: we report the effects of the antagonist fragments of human AM and CGRP (AM22-52 and CGRP8-37) in inhibiting AM at human (h), rat (r) and mixed species CL/RAMP2 and CL/...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0705472
更新日期：2003-10-01 00:00:00
abstract：:Zanapezil (TAK-147 (3-[1benzylpiperdin-4-yl]-1-(2,3,4,5-tetrahydro-1 H-1-benzazepin-8-yl) propan-1-one fumarate)) is a selective acetylcholine (ACh) esterase inhibitor under investigation as a drug for Alzheimer's disease (AD) treatment. In this study, the effects of TAK-147 at 2 mg kg(-1) p.o. for 21 days, compared t...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0706288
更新日期：2005-08-01 00:00:00
abstract：:1. To elucidate whether K+ channels play a role in the action of epithelium-dependent bronchodilatation, we studied responses in human bronchial strips in the presence of indomethacin and NG-nitro-L-arginine methylester under isometric conditions, in vitro. 2. Mechanical removal of the epithelium increased the contrac...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701183
更新日期：1997-06-01 00:00:00
abstract：:1. This study examined the impact of allopurinol on the renal functional responses to a 30 min period of ischaemia in anaesthetized rats. 2. Immediately on reperfusion, blood pressure rose transiently, while renal blood flow remained stable throughout at control values. Glomerular filtration rate was decreased by some...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702789
更新日期：1999-09-01 00:00:00
abstract：:The action of 'selective' agonists and antagonists at muscarinic receptors mediating ileal contractions, and the rate and force of atrial contractions has been assessed. The effect of nicotinic receptor stimulation, catecholamine release and acetylcholinesterase (AChE) action on muscarinic activity has also been asses...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1985.tb09446.x
更新日期：1985-09-01 00:00:00
abstract：:1. We have studied the effect of cannabinoid agonists (CP 55,940 and cannabinol) on intestinal motility in a model of intestinal inflammation (induced by oral croton oil in mice) and measured cannabinoid receptor expression, endocannabinoids (anandamide and 2-arachidonylglycerol) and anandamide amidohydrolase activity...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0704293
更新日期：2001-10-01 00:00:00
abstract：:1. The ability of the neuroprotective agent, lifarizine (RS-87476), to mitigate veratridine-, cyanide- and glutamate-induced toxicity in rat embryonic cerebrocortical neurones in primary culture has been compared with that of tetrodotoxin (TTX), nitrendipine, (+)-MK-801 and (-)-MK-801. Lactate dehydrogenase (LDH) rele...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1995.tb13357.x
更新日期：1995-04-01 00:00:00
abstract：:1 Rabbit isolated hearts, perfused by the Langendorff technique, were used to investigate the indirect sympathomimetic effects of 5-hydroxytryptamine (5-HT). Comparisons were made with noradrenaline and with two indirectly acting sympathomimetic agents with entirely different mechanisms of action, tyramine and dimethy...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1976.tb07661.x
更新日期：1976-05-01 00:00:00
abstract：:1. Sigma (sigma) receptors have generated a great deal of interest on the basis of their possible roles in various pathologies, including cytoprotection. Although the exact function of sigma-1 (sigma(1)) receptors is not yet known, their role in the regulation of intracellular Ca(2+) levels and sterol biosynthesis, fu...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0704626
更新日期：2002-04-01 00:00:00
abstract：:1. The role of adenosine 3':5'-cyclic monophosphate (cyclic AMP) in the regulation of catecholamine (CA) secretion in chromaffin cells remains equivocal from previous studies. 2. In the present study the effect of this cyclic nucleotide on basal CA secretion, as well as on intracellular calcium and membrane potential ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1995.tb13257.x
更新日期：1995-01-01 00:00:00
abstract：:1. Studies in rats suggest that PACAP modulates gastric acid secretion through the release of both histamine and somatostatin. 2. We characterized the effects of exogenous PACAP on gastric acid secretion in urethane-anesthetized mice implanted with a gastric cannula and in conscious 2-h pylorus ligated mice, and deter...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0705739
更新日期：2004-05-01 00:00:00
abstract：:1. Therapeutic doses of colistin sulphomethate sodium B.P. (Colomycin), pento-N sulphomethylpolymyxin B sodium (Thiosporin) and ampicillin B.P. (Penbritin) as well as normal saline have been given to volunteers with normal kidney function.2. A blind crossover technique was used and the effects of the compounds on bloo...
journal_title：British journal of pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1111/j.1476-5381.1969.tb09545.x
更新日期：1969-09-01 00:00:00
abstract：:The mechanism of action of prostacyclin (PGI2) on isolated segments of guinea-pig terminal ileum was studied by recording the changes in isometric tension. In these preparations PGI2 (1 nM-1 microM) caused a concentration-dependent increase in muscle tension. This effect was rapid and short-lasting. PGI2-induced contr...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1983.tb10031.x
更新日期：1983-10-01 00:00:00
abstract：:1. The influence of angiotensin II (AII) on resting blood pressure and on sympathetic nerve-mediated pressor responses in the pithed rat was investigated either by inhibiting the renin-angiotensin system or by infusing AII. 2. Plasma AII levels in the pithed rat were approximately 20 fold higher than in normotensive r...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1988.tb11759.x
更新日期：1988-12-01 00:00:00
abstract：:1 The reversible fatty acid amide hydrolase (FAAH) inhibitor OL135 reverses mechanical allodynia in the spinal nerve ligation (SNL) and mild thermal injury (MTI) models in the rat. The purpose of this study was to investigate the role of the cannabinoid and opioid systems in mediating this analgesic effect. 2 Elevated...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0706699
更新日期：2006-05-01 00:00:00
abstract：:1 Tegaserod (Zelnorm) is a potent 5-hydroxytryptamine4 (5-HT4) receptor agonist with clinical efficacy in disorders associated with reduced gastrointestinal motility and transit. The present study investigated the interaction of tegaserod with 5-HT2 receptors, and compared its potency in this respect to its 5-HT4 rece...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0705929
更新日期：2004-11-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Toll-like receptor 4 (TLR4) signalling contributes to inflammatory cardiovascular diseases, but its role in hypertension and the associated vascular damage is not known. We investigated whether TLR4 activation contributed to angiotensin II (AngII)-induced hypertension and the associated vascular ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.13117
更新日期：2015-06-01 00:00:00
abstract：:1 The effects of 4-Chloro-m-Cresol (4-CmC) were examined on heterologously expressed wild type (WT), Paramyotonia Congenita (R1448H) and Hyperkalemic Periodic Paralysis (M1360V) mutant alpha-subunits of human muscle sodium channels. 2 Block of rested sodium channels caused by 4-CmC was concentration-dependent with an ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702896
更新日期：1999-11-01 00:00:00
abstract：:1. Calcium channel blockers increase cardiovascular morbidity and mortality in patients with left ventricular dysfunction. These adverse effects are probably related to the negative inotropic effect of calcium channel blockers and/or a neurohormonal activation. 2. The present study was designed to examine, in consciou...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1994.tb17002.x
更新日期：1994-10-01 00:00:00
abstract：:1. The aim of this study was to determine the response of porcine small pulmonary arteries to intralumenal flow and to identify the cellular mechanisms and potential mediators involved in the response. 2. Porcine small pulmonary arteries were isolated from a branch of the main intrapulmonary artery of the lower lung l...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701846
更新日期：1998-05-01 00:00:00
abstract：:1. The effects of ryanodine on changes in cytoplasmic Ca2+ level ([Ca2+]i) and muscle tension induced by maximum concentrations of phenylephrine (Phe; 1 microM), prostaglandin F2 alpha (PGF2 alpha, 10 microM), caffeine (Caf, 30 mM) and isoprenaline (Iso, 1 microM) were examined in rat aortic strips using fura-2. 2. In...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1990.tb14075.x
更新日期：1990-08-01 00:00:00
