Abstract：
BACKGROUND AND PURPOSE:Dysfunction and injury of endothelial cells in the pulmonary artery play critical roles in the hypertension induced by chronic hypoxia. One consequence of hypoxia is increased activity of 15-hydroxyprostaglandin dehydrogenase (PGDH). Here, we have explored, in detail, the effects of hypoxia on the proliferation of pulmonary artery endothelial cells. EXPERIMENTAL APPROACH:We used bromodeoxyuridine incorporation, cell-cycle analysis, immunohistochemistry and Western blot analysis to study the effects of hypoxia, induced 15-PGDH) activity and its product, 15-keto-6Z, 8Z, 11Z, 13E-eicosatetraenoic acid (15-KETE), on endothelial cell proliferation. Scratch-wound and tube formation assays were also used to study migration of endothelial cells. KEY RESULTS:15-KETE increased DNA synthesis and enhanced the transition from the G0 /G1 phase to the S phase in hypoxia. Inhibition of 15-PGDH or siRNA for 15-PGDH reversed these effects. 15-KETE also activated the ERK1/2 signalling pathway. 15-KETE-induced cell migration and tube formation were reversed by blocking ERK1/2, but not the p38 MAPK pathway. CONCLUSIONS AND IMPLICATIONS:Hypoxia-induced endothelial proliferation and migration, an important underlying mechanism contributing to hypoxic pulmonary vascular remodelling, appears to be mediated by 15-PGDH and 15-KETE, via the ERK1/2 signalling pathway.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Ma C,Liu Y,Wang Y,Zhang C,Yao H,Ma J,Zhang L,Zhang D,Shen T,Zhu Ddoi
10.1111/bph.12594subject
Has Abstractpub_date
2014-07-01 00:00:00pages
3352-63issue
14eissn
0007-1188issn
1476-5381journal_volume
171pub_type
杂志文章abstract：BACKGROUND AND PURPOSE:Human lung fibroblasts (HLF) express high levels of the LPA1 receptor, a GPCR that responds to the endogenous lipid mediator, lysophosphatidic acid (LPA). Several molecular species or analogues of LPA exist and have been detected in biological fluids such as serum and plasma. The most widely expr...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.13671
更新日期：2017-02-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Alogliptin, a highly selective dipeptidyl peptidase-4 (DPP-4) inhibitor, enhances incretin action and pioglitazone enhances hepatic and peripheral insulin actions. Here, we have evaluated the effects of combining these agents in diabetic mice. EXPERIMENTAL APPROACH:Effects of short-term treatmen...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2009.00145.x
更新日期：2009-06-01 00:00:00
abstract：:1 The effect of potassium channel opening compounds has been investigated in the smooth muscle of rabbit aorta under Ca-free conditions. Examination of the characteristics of the response has been performed using cromakalim as the prototype compound. 2 In order of potency, Ro 31-6930, cromakalim, minoxidil sulphate an...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1992.tb13428.x
更新日期：1992-12-01 00:00:00
abstract：:1. Insulin antibodies were induced in young guinea-pigs of both sexes weighing 300-400 g and housed in a room maintained at 28 degrees C+/-2 degrees C, by subcutaneous injection of 2 ml of freshly prepared insulin antigen emulsion between the shoulders once every month.2. To estimate the titre of serum antibody the se...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1971.tb07087.x
更新日期：1971-05-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Ischaemia compromises mitochondrial respiration. Consequently, the mitochondrial F1 Fo-ATPsynthase reverses and acts as a proton-pumping ATPase, so maintaining the mitochondrial membrane potential (ΔΨm ), while accelerating ATP depletion and cell death. Here we have looked for a molecule that can...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.12638
更新日期：2014-09-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Endothelial cell proliferation, migration and adhesion are necessary for the formation of new blood vessels. We reported previously that baicalein strongly inhibited proliferation of rat heart endothelial cells and here we assess effects on migration and adhesion of these cells. EXPERIMENTAL APP...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0707345
更新日期：2007-08-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Histone deacetylase 6 (HDAC6) and silent information regulator 2 (SIRT2) control the dynamics of the microtubule network via their deacetylase activities. Tubulin polymerization promoting protein (TPPP/p25) enhances microtubule acetylation by its direct binding to HDAC6. Our objective was to char...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.12946
更新日期：2015-02-01 00:00:00
abstract：:1 The primary aim was to study the central respiratory effects of cannabinoids (CB). To this end, the cannabinoid receptor agonist WIN55212-2 was injected into the cisterna magna of urethane-anaesthetised rats and changes in respiratory parameters were observed. The secondary aim was to observe the centrally elicited ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0705874
更新日期：2004-07-01 00:00:00
abstract：:1. Whole-cell patch-clamp recordings were made from smooth muscle cells isolated from the longitudinal muscle layer of guinea-pig ileum. Carbachol (acting at muscarinic receptors) or histamine (acting at H1 histamine receptors) suppressed Ca2+ channel current. The effect of either agonist had an initial transient comp...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702112
更新日期：1998-10-01 00:00:00
abstract：:1. The novel bradykinin antagonist, HOE 140, completely blocked the fall in rabbit blood pressure caused, not only by i.v. bradykinin, but also by i.v. kallikrein. This shows that both the effects of exogenously administered bradykinin and those of endogenously released kinins are antagonized by HOE 140. 2. Acute panc...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1992.tb12751.x
更新日期：1992-10-01 00:00:00
abstract：:1. The effect of the potassium channel openers, NIP-121 and cromakalim, on agonist-induced relaxation of the guinea-pig isolated trachea was investigated and the results were compared with those in the epithelium-denuded trachea. 2. Tracheal strips were incubated with a potassium channel opener or vehicle for 30 min i...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1992.tb13416.x
更新日期：1992-12-01 00:00:00
abstract：BACKGROUND AND PURPOSE:In mammalian cells, the anti-parasitic drug ivermectin is known as a positive allosteric modulator of the ATP-activated ion channel P2X4 and is used to discriminate between P2X4- and P2X7-mediated cellular responses. In this paper we provide evidence that the reported isoform selectivity of iverm...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2012.01987.x
更新日期：2012-09-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Diabetes is a risk factor for the development of coronary artery disease but it is not known whether the functions of endothelium-derived nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) in coronary arteries are altered in the early stage of diabetes. Such alterations and t...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2009.00348.x
更新日期：2009-09-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Sepsis is a systemic inflammatory response accompanied by excessive production of inflammatory cytokines and cardiovascular dysfunction. Importantly, macrophage-derived pro-inflammatory agents play a key role in cardiovascular impairment in sepsis. Here we have investigated the effects of trimeta...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.13386
更新日期：2016-02-01 00:00:00
abstract：:1. The present study was undertaken to investigate the effect of Delta9-tetrahydrocannabinol (Delta9-THC) and possible serotoninergic involvement on the extracellular level of dopamine (DA) in the striatum using microdialysis in conscious, freely-moving rats. 2. A dose-dependent increase in striatal DA release occurre...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702753
更新日期：1999-09-01 00:00:00
abstract：:The muscarinic receptor binding of trazodone, a new nontricyclic antidepressant, was compared with established tricyclic antidepressants. The ability to inhibit the binding of [3H]-quinuclidinyl benzilate in vitro was used for comparing atropine-like effects. Trazodone was found to have essentially no activity at the ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1980.tb10947.x
更新日期：1980-01-01 00:00:00
abstract：:1. Thoracic aortae, isolated from rats supplemented with dietary vitamin E after vitamin E deficiency, were analysed for changes in vascular reactivity. 2. Following 4 or 12 months of dietary vitamin E deficiency, endothelium-dependent vasodilator responses to acetylcholine were significantly impaired. However, when a...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1994.tb13103.x
更新日期：1994-06-01 00:00:00
abstract：:1. Daily i.p. administration, for eight days, of the cholinesterase inhibitor disulfoton to rats produced mild to moderate signs of intoxication (tremors, incontinence and diarrhoea) but no deaths.2. Segments of ileum taken from the treated rats were subsensitive to carbachol but the vas deferens and the uterus did no...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1973.tb08350.x
更新日期：1973-07-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Intestinal mucositis is a common side-effect of irinotecan-based cancer chemotherapy regimens. This mucositis is associated with cytokine activation and NO synthesis. Production of IL-18 is up-regulated in patients suffering from inflammatory bowel disease. Therefore, we have investigated the rol...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.12584
更新日期：2014-05-01 00:00:00
abstract：:1. We studied the effects of various K+ channel blockers on the vasodilator responses of guinea-pig isolated basilar arteries to nitrergic nerve stimulation, the nitric oxide (NO) donor sodium nitroprusside (SNP), and the membrane permeable guanosine-3',5'-cyclic monophosphate (cyclic GMP) analogue 8-bromo-cyclic GMP ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701552
更新日期：1998-01-01 00:00:00
abstract：:1. The subtype of alpha1-adrenoceptor mediating contractions to phenylephrine of the rat thoracic aorta, mesenteric artery and pulmonary artery were investigated by use of antagonists which show selectivity between the cloned alpha1-adrenoceptor subtypes in binding studies. 2. Cumulative concentration-contraction curv...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701461
更新日期：1997-11-01 00:00:00
abstract：:LDL cholesterol (LDL-C) plays a central role in the progression of atherosclerosis. Statin therapy for lowering LDL-C reduces the risk of atherosclerotic cardiovascular disease and is the recommended first-line treatment for patients with high LDL-C levels. However, some patients are unable to achieve an adequate redu...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.14851
更新日期：2019-08-29 00:00:00
abstract：:1 The effects of a subconstrictor dose of histamine (9 x 10(-7) mol/l) on the responses of the isolated perfused ear artery of the rabbit to electrical stimulation (E.S.) and to exogenous noradrenaline (NA) were investigated.2 Both intraluminal (I/L) and extraluminal (E/L) histamine potentiated responses to E.S. and t...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1979.tb08684.x
更新日期：1979-11-01 00:00:00
abstract：:1 Inactivation of prostaglandin E2 in the pulmonary circulation of rabbits in vivo was measured by comparing the hypotensive effects of doses given intravenously and intra-arterially. 2 Di-4-phloretin phosphate (DPP) 25-100 mug kg-1 min-1 inhibited the inactivation of prostaglandin E2 in the pulmonary circulation. 3 T...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1975.tb07569.x
更新日期：1975-07-01 00:00:00
abstract：:NO is a neurotransmitter released from enteric inhibitory neurons and responsible for modulating gastrointestinal (GI) motor behaviour. Enteric neurons express nNOS (NOS1) that associates with membranes of nerve varicosities. NO released from neurons binds to soluble guanylate cyclase in post-junctional cells to gener...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.14459
更新日期：2019-01-01 00:00:00
abstract：:1. The mechanism by which neuropeptide Y (NPY) potentiates the vasoconstriction induced by alpha 1-adrenoceptor agonists was investigated in 3rd generation mesenteric arterioles of the rat. 2. At a maximally active concentration, nitrendipine (10(-6) M) displaced to the right the concentration-response curves to norad...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1990.tb14714.x
更新日期：1990-02-01 00:00:00
abstract：:1. Intrathecal (i.t.) administration of nociceptin and high doses of morphine induced allodynia in response to innocuous tactile stimuli, and i.t. nociceptin evoked hyperalgesia in response to noxious thermal stimuli in conscious mice. Here we have characterized the nociceptin-induced allodynia and compared it with th...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701146
更新日期：1997-06-01 00:00:00
abstract：:1 The possible involvement of N-methyl-D-aspartate (NMDA)-receptors in epileptiform synaptic activity in the kainic acid (KA) lesioned hippocampus was investigated. In this chronic model of epilepsy there is a loss of both the early and the late components of synaptic inhibition as well as changes in the membrane prop...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1987.tb11280.x
更新日期：1987-08-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Cannabis extracts and several cannabinoids have been shown to exert broad anti-inflammatory activities in experimental models of inflammatory CNS degenerative diseases. Clinical use of many cannabinoids is limited by their psychotropic effects. However, phytocannabinoids like cannabidiol (CBD), d...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2011.01379.x
更新日期：2011-08-01 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
