Abstract:
:1. Vascular endothelial and smooth muscle cells generate nitric oxide (NO) via different nitric oxide synthase (NOS) isozymes. Activation of the endothelial constitutive NOS (ecNOS) contributes to the maintenance of cardiovascular homeostasis, whereas expression of the endotoxin- and cytokine-inducible pathway (iNOS) within the vascular smooth muscle is thought to be responsible for the cardiovascular collapse which occurs during septic shock and antitumour therapy with cytokines. Since the cytoskeleton is involved in the activation of certain genes and in some effects of endotoxin in macrophages, we investigated the role of microtubules and microfilaments in the activation of the NO pathway in cultured vascular cells. 2. Depolymerization of microtubules by either nocodazole or colchicine prevented lipopolysaccharide (LPS)- and interleukin-1 beta-induction of NO-dependent cyclic GMP accumulation. Steady state levels of iNOS mRNA, assessed by Northern blot and RT-PCR, and iNOS protein, assessed by Western blotting, were also decreased by either colchicine or nocodazole treatment. 3. Taxol enhanced microtubule polymerization alone, and prevented microtubule depolymerization elicited by nocodazole and colchicine. Associated with its effect on microtubule assembly, taxol prevented the inhibitory effects of nocodazole and colchicine on cyclic GMP accumulation and iNOS mRNA levels. 4. Disruption of microfilaments by cytochalasins had no inhibitory effect on the activation of the inducible NO pathway. 5. In contrast to cytokine-stimulated smooth muscle cells, modulation of either microtubule or microfilament assembly did not affect the constitutive NO pathway in endothelial cells, as endothelial cell- and NO-dependent cyclic GMP accumulation in endothelial-smooth muscle co-cultures remained unchanged. 6. Our findings demonstrate that microtubules play a prominent role in the activation of the inducible NO pathway in response to inflammatory mediators in smooth muscle cells but not of the constitutive synthesis of NO in endothelial cells.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Marczin N,Jilling T,Papapetropoulos A,Go C,Catravas JDdoi
10.1111/j.1476-5381.1996.tb15510.xsubject
Has Abstractpub_date
1996-07-01 00:00:00pages
1085-94issue
5eissn
0007-1188issn
1476-5381journal_volume
118pub_type
杂志文章abstract:BACKGROUND AND PURPOSE:Inhaled glucocorticoid (ICS)/long-acting β2 -adrenoceptor agonist (LABA) combination therapy is a recommended treatment option for patients with moderate/severe asthma in whom adequate control cannot be achieved by an ICS alone. Previously, we discovered that LABAs can augment dexamethasone-induc...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.13087
更新日期:2015-05-01 00:00:00
abstract::1. Prostaglandin F2 alpha (PGF2 alpha) and its synthetic analogue, fluprostenol, potently relaxed the precontracted isolated jugular vein of the rabbit (RJuV). The vasorelaxant activity of PGF2 alpha and fluprostenol was dependent upon an intact vascular endothelium. Although removal of the vascular endothelium abolis...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb15960.x
更新日期:1995-12-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Toll-like receptor 4 (TLR4) plays a key role in the induction of inflammatory responses both in peripheral organs and the CNS. Curcumin exerts anti-inflammatory functions by interfering with LPS-induced dimerization of TLR4-myeloid differentiation protein-2 (MD-2) complex and suppressing pro-infl...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.13746
更新日期:2017-05-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Microglial phenotype and phagocytic activity are deregulated in Parkinson's disease (PD). PPARγ agonists are neuroprotective in experimental PD, but their role in regulating microglial phenotype and phagocytosis has been poorly investigated. We addressed it by using the PPARγ agonist MDG548. EXP...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.14214
更新日期:2018-08-01 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::1. The NK1 tachykinin receptor agonists, septide, [Sar9,Met(O2)11]SP and [Pro9]SP produced locomotor hyperactivity (10-20 min) when injected intracerebroventricularly (i.c.v.) in the guinea-pig. The most potent in eliciting this hyperactivity was septide (from 0.63 to 5 micrograms), compared to [Sar9,Met(O2)11]SP, whi...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb15101.x
更新日期:1995-11-01 00:00:00
abstract::Cyclo-oxygenase (COX) inhibitors potentiate opioid inhibition of GABAergic synaptic transmission in rat periaqueductal grey (PAG) (Vaughan et al., 1997). In the present study, the relative contribution of cyclo-oxygenase-1 (COX-1) and COX-2 inhibition to this phenomenon was examined by use of whole-cell patch clamp re...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701818
更新日期:1998-04-01 00:00:00
abstract::1. In pithed rats, preganglionic vagal nerve stimulation (at 5 Hz) elicited a bradycardia. This bradycardia was potentiated by the angiotensin converting enzyme inhibitor, captopril (1 mg kg-1, i.v.) by about 40%. Subsequent angiotensin II infusion (0.03 micrograms kg-1 min-1) reversed this effect. A similar facilitat...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1993.tb13807.x
更新日期:1993-09-01 00:00:00
abstract::1. The pharmacological profile of LR-B/081, (methyl 2-[[4-butyl-2-methyl- 6-oxo-5-[[2'-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]-1(6H)- pyrimidinyl]methyl]-3-thiophenecarboxylate), a novel antagonist at the angiotensin II (AII) AT1-receptor, was studied in vitro and in vivo. 2. In rabbit aortic strips incubated w...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb13323.x
更新日期:1995-03-01 00:00:00
abstract::1. The rate of gastric emptying was measured directly in 14 convalescent hospital patients and paracetamol absorption was studied following an oral dose of 1.5 g.2. Rapid gastric emptying was associated with the early appearance of high peak plasma paracetamol concentrations whereas peak concentrations were low and oc...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1973.tb08339.x
更新日期:1973-02-01 00:00:00
abstract::1 The effects of the putative 5-hydroxytryptamine (5-HT) receptor antagonists, methysergide, mianserin and methergoline, the dopamine receptor antagonists, haloperidol, thioridazine and clozapine, and the noradrenaline (NA) receptor antagonists, phentolamine, phenoxybenzamine and propranolol on the behavioural respons...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1982.tb09278.x
更新日期:1982-09-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Uridine 5'-triphosphate (UTP) is a potent vasoconstrictor of cerebral arteries and induces Ca(2+) waves in vascular smooth muscle cells (VSMCs). This study aimed to determine the mechanisms underlying UTP-induced Ca(2+) waves in VSMCs of the rat basilar artery. EXPERIMENTAL APPROACH:Isometric fo...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2008.00063.x
更新日期:2009-02-01 00:00:00
abstract::1. Acetylcholine (ACh)-induced relaxation of aortic strips with endothelium and production of cyclic GMP between streptozotocin-induced diabetic and age-matched control rats were compared. 2. The concentration-response curve for ACh-induced relaxation was shifted to the right in diabetic rats. IC50 values for ACh were...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1989.tb11993.x
更新日期:1989-06-01 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::The effects of histamine and of H1- and H2-receptor agonists on the response to specific antigen were studied in isolated hearts taken from actively sensitized guinea-pigs. Histamine and H2-receptor agonists (dimaprit, impromidine) dose-dependently decrease the positive chronotropic and inotropic effects, and the seve...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1987.tb11195.x
更新日期:1987-03-01 00:00:00
abstract::1. Conventional microelectrode techniques were used for intracellular recordings of the transmembrane electrical potentials, the effects of berberine were studied on canine cardiac Purkinje and ventricular muscle fibres and on rabbit atrial fibres. 2. Berberine (3-30 microM) increased in a concentration-dependent mann...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1993.tb12836.x
更新日期:1993-02-01 00:00:00
abstract:BACKGROUND AND PURPOSE:GABAA receptors mediate neuronal inhibition in the brain. They are the primary targets for benzodiazepines, which are widely used to treat neurological disorders including anxiety, epilepsy and insomnia. The mechanism by which benzodiazepines enhance GABAA receptor activity has been extensively s...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.13142
更新日期:2015-07-01 00:00:00
abstract::1. Bradykinin (BK) instilled directly into the airway lumen caused bronchoconstriction in anaesthetized, mechanically ventilated guinea-pigs in the presence of propranolol (1 mg kg-1 i.v.). The geometric mean dose of BK required to produce 100% increase in airway opening pressure (PD100) was 22.9 nmol (95% c.i. 11.7-4...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1990.tb12092.x
更新日期:1990-09-01 00:00:00
abstract::1. The effects of dopamine on the L-type Ca2+ current (ICa,L) of both atrial and ventricular single myocytes and on the force of contraction of atrial trabeculae in rat heart were investigated. 2. Dopamine increased atrial ICa,L at concentrations higher than 1 microM, but had little or no effect on ICa,L at lower conc...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701250
更新日期:1997-08-01 00:00:00
abstract::1. Previous work from our laboratory has shown that cannabis induces aggressive behaviour in rats that have been deprived of rapid eye movement (REM) sleep. It was suggested that this effect was related to brain catecholamines, with dopamine playing an agonist role and noradrenaline an inhibitory one. The present pape...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1977.tb08429.x
更新日期:1977-11-01 00:00:00
abstract::1 The rectum isolated from the fowl was perfused with Tyrode solution via the caudal mesenteric artery. Noradrenaline and adrenaline were biologically or fluorimetrically assayed in perfusates collected before and during stimulation of Remak's nerve or of the periarterial nerves.2 Perfusates collected during nerve sti...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1979.tb07827.x
更新日期:1979-02-01 00:00:00
abstract::1. Intravenous administration of leukotriene C4 (LTC4) and LTD4 (1-10 nmol kg-1) caused a dose-dependent increase in secretion of glandular-kallikrein in the bronchial washings of guinea-pigs, as measured by cleavage of a synthetic substrate and the formation of kinin. LTC4 was more potent than LTD4 and pilocarpine wa...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1992.tb09031.x
更新日期:1992-03-01 00:00:00
abstract::1. Aqueous extracts of stratum corneum were found to cause histamine-like contractions of the guinea-pig ileum which were not antagonized by mepyramine, atropine or bromolysergic acid diethylamide.2. The compounds responsible for this contraction were isolated by chromatography and shown to be common amino acids, part...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1972.tb09581.x
更新日期:1972-05-01 00:00:00
abstract::We have examined whether modulation of the polyamine biosynthetic pathway, through inhibition by alpha-difluoromethylornithine (DFMO) of the rate limiting enzyme, ornithine decarboxylase (ODC), modulates NO synthesis in J774 macrophages. DFMO potentiated LPS-stimulated nitrite production in both a concentration- and t...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702231
更新日期:1998-12-01 00:00:00
abstract::The last five years have witnessed a remarkable resurgence of interest in myocardial reperfusion injury. Reperfusion is absolutely essential to salvage ischaemic myocardium but experimental and clinical studies show that reperfusion-associated injury may mask the full benefits of prompt reperfusion in acute myocardial...
journal_title:British journal of pharmacology
pub_type: 评论,杂志文章
doi:10.1038/sj.bjp.0707498
更新日期:2008-01-01 00:00:00
abstract::1. The effects of the muscarinic agonist carbachol on phosphoinositide metabolism and its relationship to alteration of intracellular calcium were examined in SK-N-SH human neuroblastoma cells. Muscarinic receptors on these cells are coupled to phospholipase C and the myo [2-3H]-inositol phosphates resulting from rece...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1989.tb12681.x
更新日期:1989-12-01 00:00:00
abstract::1. The involvement of nitric oxide (NO) in the regulation of angiogenesis was examined in the in vivo system of the chorioallantoic membrane (CAM) of the chick embryo and in the matrigel tube formation assay. 2. Sodium nitroprusside (SNP) (0.37-28 nmol/disc), which releases NO spontaneously, caused a dose-dependent in...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1994.tb14822.x
更新日期:1994-03-01 00:00:00
abstract::1. A study has been made of serum, mixed and parotid salivary levels attained in normal volunteers following oral dosage of 500 mg phenoxymethylpenicillin tablets, 500 mg crushed phenoxymethylpenicillin tablets in capsules, 500 mg ampicillin, 500 mg cloxacillin and 500 mg cephalexin.2. High mixed saliva levels were ob...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1971.tb07173.x
更新日期:1971-09-01 00:00:00
abstract::1. An investigation into the effects of cholecystokinin octapeptide (CCK-8S) and its pentapeptide analogue, pentagastrin, on neurones located in ventromedial nuclei of rat hypothalamic slices maintained in vitro has been undertaken. 2. CCK-8S (0.01-1.0 microM) applied in the perfusion medium produced a concentration-d...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1988.tb11521.x
更新日期:1988-05-01 00:00:00
abstract::The effect of acute, streptozotocin-induced diabetes on the affinity (KD), density (Bmax) and selectivity of specific, high affinity binding sites for [125I]-endothelin [( 125I]-ET) in rat cardiac membrane fragments was determined. Three days after a single i.v. bolus dose of streptozotocin (60 mg kg-1), the density o...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1989.tb12552.x
更新日期:1989-08-01 00:00:00