Abstract：
:1. Elevated plasminogen activator inhibitor 1 (PAI-1) is a risk factor for thrombosis, and inhibitors of the interaction between PAI-1 and tissue plasminogen activator (t-PA) have antithrombotic and prothrombolytic activity in animals. We describe the antithrombotic effects in the rat of a monoclonal antibody (MA33H1) which converts PAI-1 to a non-inhibitory substrate. 2. The activity of MA33H1 against rat PAI-1 was confirmed using two-chain t-PA and a chromogenic substrate. MA33H1 was evaluated in rat venous (thromboplastin + stasis in the abdominal vena cava) and arterial (electric current applied to a carotid artery) thrombosis models. The effects on tail-transection bleeding time were studied. 3. MA33H1 at 100 ng ml(-1) inhibited both human (44.1%) and rat PAI-1 (49.7%). This effect was concentration-dependent. Its effect on human PAI-1 was not significantly inhibited by 1 microg ml(-1) fibrin or a approximately 7 fold molar excess of vitronectin (1 nM). Inhibition of rat PAI-1 was unchanged by fibrin, but vitronectin reduced inhibition from 0.5 nM. 4. In the venous thrombosis model, MA33H1 significantly reduced thrombus weights by 38 and 58.6% at 50 and 100 microg kg(-1) min(-1) i.v. respectively. This effect was inhibited by tranexamic acid. In the arterial model, MA33H1 significantly increased the delay to occlusive thrombus formation by 58 and 142% at 50 and 100 microg kg(-1) min(-1) i.v., and did not affect bleeding time at 300 microg kg(-1) min(-1) i.v. 5. Thus, a monoclonal antibody which transforms PAI-1 to a t-PA substrate prevents thrombus formation in the rat with no effect on bleeding time at a higher dose.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Berry CN,Lunven C,Lechaire I,Girardot C,O'Connor SEdoi
10.1038/sj.bjp.0702030subject
Has Abstractpub_date
1998-09-01 00:00:00pages
29-34issue
1eissn
0007-1188issn
1476-5381journal_volume
125pub_type
杂志文章abstract：:1 Cumulative concentration-response relationships for the chronotropic effects of histamine, oxymetazoline, clonidine and thirteen clonidine-like imidazolidine derivatives were examined in isolated spontaneously beating guinea-pig atria.2 The following compounds induced positive chronotropic effects: histamine, clonid...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1980.tb07028.x
更新日期：1980-07-01 00:00:00
abstract：:1 PD 117302, a new nonpeptide opioid compound shown in in vitro studies to be a selective kappa-opioid agonist, has been evaluated in vivo for antinociceptive activity and other effects characteristic of kappa-receptor activation. 2 Dose-related long lasting antinociception was produced by PD 117302 against a mechanic...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1987.tb11398.x
更新日期：1987-12-01 00:00:00
abstract：:1 Amodiaquine was found to be a potent inhibitor in vitro of gastric histamine methyltransferase from human and canine corpus and from pig antrum. The ID50 for the enzyme, purified from pig antrum mucosa by ultracentrifugation and chromatography on DEAE-cellulose, was 2.5 muM. 2 In six dogs with Heidenhanin pouches th...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1975.tb06934.x
更新日期：1975-11-01 00:00:00
abstract：:Ischaemia is amongst the leading causes of death. Despite this importance, there are only a few therapeutic approaches to protect from ischaemia-reperfusion injury (IRI). In experimental studies, the amino acid glycine effectively protected from IRI. In the prevention of IRI by glycine in cells and isolated perfused o...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/j.1476-5381.2011.01711.x
更新日期：2012-04-01 00:00:00
abstract：:1 The activity and pulmonary metabolism of two peptides, 7-homo Pro-bradykinin and 8-homo Phe-bradykinin were studied in isolated systems. 2 Both analogues were about 50-70 times less active than bradykinin on the guinea-pig ileum and 70-160 times less active on isolated strips of cat terminal ileum. 3 The action of b...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1977.tb06985.x
更新日期：1977-01-01 00:00:00
abstract：:A new canine model of endotoxin shock has been developed in which spontaneous recovery of cardiovascular function is largely prevented, the haemodynamic effects of anaesthesia are minimized and intravascular volume replacement is given. This model has been evaluated using two groups of five adult mongrel dogs anaesthe...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1984.tb16504.x
更新日期：1984-10-01 00:00:00
abstract：:1. Effects of oestradiol on the electrical and mechanical properties of the rabbit basilar artery were investigated by use of microelectrode, patch-clamp and isometric tension recording methods. 2. Oestradiol (10 nM-100 microM) relaxed arterial tissue pre-contracted by excess [K]o solution (30 mM) in a concentration-d...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1996.tb15198.x
更新日期：1996-01-01 00:00:00
abstract：:The electrically-evoked contractions of the rat vas deferens were selectively inhibited by beta-endorphin, the preparation being much less sensitive to enkephalins and narcotic analgesic drugs. However, introduction of D-Ala in position 2 of [Leu]-enkephalin enhanced the activity of the opioid peptide to the order of ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1978.tb08653.x
更新日期：1978-11-01 00:00:00
abstract：:5-Hydroxytryptamine (5-HT) evoked potent contractile responses in phenoxybenzamine-treated ring segments of rat caudal artery, partially contracted with U46619. Responses were mimicked by 5-HT1-selective agonists with the potency order: RU24969 > 5-carboxamidotryptamine > 5-HT = CP-93,129 > sumatriptan. 8-Hydroxy-N,N-...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1993.tb13615.x
更新日期：1993-07-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Melanocortins reverse circulatory shock and improve survival by counteracting the systemic inflammatory response, and through the activation of the vagus nerve-mediated cholinergic anti-inflammatory pathway. To gain insight into the potential therapeutic value of melanocortins against multiple or...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2010.01098.x
更新日期：2011-02-01 00:00:00
abstract：:The neonate has an unusual capacity for survival and the possibility exists that mechanisms for controlling stress responses may differ in the developing animal. In adults both endogenous and exogenous opioids can modulate the corticosterone responses to stress. We have studied this effect in neonatal rats and found t...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1987.tb08990.x
更新日期：1987-05-01 00:00:00
abstract：:1. Histamine release by compound 48/80 was substantially reduced in a time-dependent manner (maximum at 30 min) by pre-incubating mast cells in calcium-free medium at 37 degrees C but not at 2 degrees C. This effect was optimal at pH 7.0 to 7.5. 2. The re-introduction of calcium (0.1 to 3 mmol/l) restored histamine re...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1979.tb07871.x
更新日期：1979-04-01 00:00:00
abstract：:1. The effects of bretylium have been investigated on the content and sub-cellular distribution of noradrenaline in cat spleen and on the overflow of noradrenaline in response to stimulation of the splenic nerve.2. Bretylium, 15 min after its administration, produces a significant depletion of noradrenaline in only th...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1970.tb09887.x
更新日期：1970-04-01 00:00:00
abstract：:The effect of docosahexaenoic acid (DHA) on nitric oxide (NO) production and inducible NO synthase (iNOS) expression induced by interleukin (IL)-1beta, and whether the effect of DHA is related to its effect on mitogen-activated protein kinase (MAPK) activation were investigated in cultured rat vascular smooth muscle c...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0704768
更新日期：2002-06-01 00:00:00
abstract：:1. The modification by Bay K 8644 of the vasodilator effects of nifedipine, diltiazem, nicorandil and nitroglycerin was investigated in the femoral arterial bed of anaesthetized dogs. 2. The right femoral artery was cannulated and its arterial bed was perfused with autologous blood at a constant pressure slightly high...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1988.tb11415.x
更新日期：1988-01-01 00:00:00
abstract：:In the clinic, low efficacy positive GABAA modulators might be preferred to high efficacy positive modulators insofar as low efficacy modulators might have comparatively less abuse and dependence liability. Drug discrimination was used to examine the behavioral effects of L-838,417 and bretazenil, two low efficacy pos...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0706550
更新日期：2006-02-01 00:00:00
abstract：:The binding of DL-[3,4-3H] 2-amino-4-phosphonobutyric acid DL[3H]-APB to rat whole brain synaptic membranes was investigated. Binding was linear with membrane protein concentration, and optimal at physiological pH and temperature. The association rate was rapid, achieving equilibrium within 10 min. Prolonged incubatio...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1983.tb10041.x
更新日期：1983-10-01 00:00:00
abstract：LINKED ARTICLES:This article is part of a themed section on Nitric Oxide 20 Years from the 1998 Nobel Prize. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.2/issuetoc. ...
journal_title：British journal of pharmacology
pub_type： 社论
doi：10.1111/bph.14540
更新日期：2019-01-01 00:00:00
abstract：:Pulmonary hypertension (PH) is a rare, progressive pulmonary vasculopathy characterized by increased mean pulmonary arterial pressure, pulmonary vascular remodelling and right ventricular failure. Current treatments are not curative, and new therapeutic strategies are urgently required. Clinical and preclinical eviden...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.14375
更新日期：2019-06-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Voltage-gated sodium channels (VGSCs) are assembled from two classes of subunits, a pore-bearing α-subunit (NaV 1) and one or two accessory β-subunits (NaV βs). Neurons in mammals can express one or more of seven isoforms of NaV 1 and one or more of four isoforms of NaV β. The peptide μ-conotoxin...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.12051
更新日期：2013-04-01 00:00:00
abstract：:1. Bradykinin (BK) and Lys-BK are peptides which are released at high nanomolar concentrations into the tear-film of ocular allergic patients. We hypothesized that these peptides may activate specific receptors on the ocular surface, especially the corneal epithelium (CE) and thus the CE cells may represent a potentia...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701168
更新日期：1997-06-01 00:00:00
abstract：:1. The present study addressed the role of neuropeptide (NPY) Y2 receptors in neurogenic contraction of mesenteric resistance arteries from female spontaneously hypertensive rats (SHR). Arteries were suspended in microvascular myographs, electrical field stimulation (EFS) was performed, and protein evaluated by Wester...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0706774
更新日期：2006-07-01 00:00:00
abstract：:1. Patients with airway infection by Pseudomonas aeruginosa have impaired mucociliary clearance. Pyocyanin is a phenazine pigment produced by P. aeruginosa which is present in the sputum of colonized patients, slows human ciliary beat frequency (CBF) in vitro and slows mucociliary transport in vivo in the guinea-pig. ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1994.tb13100.x
更新日期：1994-06-01 00:00:00
abstract：:The Wnt/β-catenin signalling pathway is pivotal for stem cell function and the control of cellular differentiation, both during embryonic development and tissue homeostasis in adults. Its activity is carefully controlled through the concerted interactions of concentration-limited pathway components and a wide range of...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.14038
更新日期：2017-12-01 00:00:00
abstract：:1 The effects of electrical stimulation, changes in external ion concentrations and various drugs on acetylcholine release from the myenteric plexus were measured by bioassay in the presence of physostigmine and by recording the responses of the longitudinal muscle. In preparations from the guinea-pig, the acetylcholi...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1978.tb17319.x
更新日期：1978-12-01 00:00:00
abstract：:1. Fluoxetine (Prozac) is widely used as an antidepressant drug and is assumed to be a selective 5-hydroxytryptamine (5-HT) reuptake inhibitor (SSRI). Claims that its beneficial psychotropic effects extend beyond those in treatment of depression have drawn clinical and popular attention to this compound, raising the q...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701545
更新日期：1997-12-01 00:00:00
abstract：:Class A1 scavenger receptors (SR-A1) are membrane glycoproteins that can form homotrimers. This receptor was originally defined by its ability to mediate the accumulation of lipids in macrophages. Subsequent studies reveal that SR-A1 plays critical roles in innate immunity, cell apoptosis and proliferation. This revie...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.13105
更新日期：2015-12-01 00:00:00
abstract：:1. The effect of bradykinin on the Na+-K+ pump of airway smooth muscle was investigated by measuring ouabain-sensitive (86)Rb(+) uptake in cultured guinea-pig tracheal smooth muscle cells. 2. Bradykinin induced a concentration-dependent increase in ouabain-sensitive (86)Rb(+) uptake, with an EC(50) of 3 nM (pD(2) = 8....
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0704198
更新日期：2001-08-01 00:00:00
abstract：:1 The influence of dopamine receptor agonists on gastric acid secretion stimulated by thyrotropin-releasing hormone (TRH) was studied in the perfused stomach of anaesthetized rats. 2 Intraventricular TRH produced a dose-dependent stimulation of basal gastric acid secretion. 3 Pretreatment with apomorphine, bromocripti...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1983.tb10524.x
更新日期：1983-05-01 00:00:00
abstract：:1. Photoactivated mechanical responses that resulted from exposure to 3-NO2-1,4-dihydropyridines (3-NO2-DHP5) or NO-donors were examined in rat isolated oesophageal smooth muscle with a view to determining the role of calcium and cyclic GMP. 2. Isometric contractile force was recorded in preparations bathed in normal ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1995.tb15138.x
更新日期：1995-12-01 00:00:00
