Abstract：
:Cartilage destruction is a key characteristic of arthritic disease, a process now widely established to be mediated by metzincins such as MMPs. Despite showing promise in preclinical trials during the 1990s, MMP inhibitors for the blockade of extracellular matrix turnover in the treatment of cancer and arthritis failed clinically, primarily due to poor selectivity for target MMPs. In recent years, roles for serine proteinases in the proteolytic cascades leading to cartilage destruction have become increasingly apparent, renewing interest in the potential for new therapeutic strategies that utilize pharmacological inhibitors against this class of proteinases. Herein, we describe key serine proteinases with likely importance in arthritic disease and highlight recent advances in this field. LINKED ARTICLES: This article is part of a themed section on Translating the Matrix. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.1/issuetoc.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Wilkinson DJ,Arques MDC,Huesa C,Rowan ADdoi
10.1111/bph.14173subject
Has Abstractpub_date
2019-01-01 00:00:00pages
38-51issue
1eissn
0007-1188issn
1476-5381journal_volume
176pub_type
杂志文章,评审abstract：:Amyotrophic lateral sclerosis (ALS) is an adult onset disorder characterized by progressive neuromuscular junction (NMJ) dismantling and degeneration of motor neurons leading to atrophy and paralysis of voluntary muscles responsible for motion and breathing. Except for a minority of patients harbouring genetic mutatio...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.15276
更新日期：2020-09-28 00:00:00
abstract：:1. In order to investigate the modulatory effects of adenosine on excitatory amino acid projections onto striatal medium spiny neurons, whole-cell patch clamp experiments were carried out in rat brain slices. The effects of various agonists for P1 (adenosine) and P2 (ATP) purinoceptors and their antagonists were inves...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701347
更新日期：1997-09-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Increased level of very low-density lipoprotein (VLDL) is a key feature of the metabolic syndrome and is associated with cardiovascular diseases. PPAR-δ agonists play a protective role in lipid metabolism and vascular function. In this study, we aimed to investigate the role of PPAR-δ in the upta...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.13160
更新日期：2015-08-01 00:00:00
abstract：:1. Inhibition of human polymorphonuclear leucocyte (PMN) function by adenosine was studied with respect to effects of adenosine on intracellular cyclic AMP and calcium during the PMN respiratory burst. 2. The adenosine analogue 5'-N-ethylcarboxamide-adenosine (NECA) and L-N6-phenyl-isopropyl-adenosine (L-PIA) inhibite...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1989.tb12028.x
更新日期：1989-07-01 00:00:00
abstract：:1. Heptaminol stopped or delayed the progressive decline in tension which characterizes the phenomenon of fatigue in frog isolated twitch muscle fibre. 2. Heptaminol had no action on the sodium, potassium and calcium voltage-dependent ionic conductances. 3. The hypothesis of an action via an internal alkalinization wa...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1991.tb12493.x
更新日期：1991-11-01 00:00:00
abstract：:1. Antipsychotic drugs may mediate their therapeutic effects not only by preventing the binding of dopamine but also by decreasing the propensity of the dopamine receptor to assume an active R* state. Ligand-mediated activation and blockade of the recombinant human D(2long) receptor was investigated in CHO-K1 cells up...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0704243
更新日期：2001-09-01 00:00:00
abstract：:1. The inhibitory effect of erythrocyte suspensions and haemoglobin solutions on the response of the bovine retractor penis muscle (BRP) and the rat anococcygeus to field stimulation of their non-adrenergic non-cholinergic (NANC) nerves has been compared. Haemoglobin 3 microM greatly reduced the relaxant response in b...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1989.tb12616.x
更新日期：1989-10-01 00:00:00
abstract：BACKGROUND AND PURPOSE:beta-Amyloid peptide (Abeta) is implicated in the pathogenesis of Alzheimer's disease by initiating a cascade of events from mitochondrial dysfunction to neuronal death. The metabolic enhancer piracetam has been shown to improve mitochondrial dysfunction following brain aging and experimentally i...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2010.00656.x
更新日期：2010-05-01 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：:1 The concentrations of p- and m-tyramine, dopamine and homovanillic acid were measured in the mouse striatum following the subcutaneous administration of amfonelic acid, (+)-amphetamine or nomifensine.2 The administration of 2.5-25 mg/kg of amfonelic acid produced a reduction in p-tyramine that lasted at least 8 h. m...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1982.tb09325.x
更新日期：1982-11-01 00:00:00
abstract：:The diterpene, forskolin, is shown to produce a concentration-dependent, increase in short circuit current in two epithelial preparations, amphibian skin and rat colon. In the amphibian tissue the increase is sensitive to amiloride and due to an increase in electrogenic transepithelial sodium transport towards the ser...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1982.tb09187.x
更新日期：1982-05-01 00:00:00
abstract：:1. Electrical stimulation of the mid-brain raphé in anaesthetized adrenalectomized rats produced a significant decrease in the forebrain content of 5-hydroxytryptamine (5-HT) and an increase in the concentration of 5-hydroxyindol-3-ylacetic acid (5-HIAA).2. Stimulation of peripheral sensory nerves did not influence ei...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1970.tb09550.x
更新日期：1970-05-01 00:00:00
abstract：:1. Stimulation of the murine macrophage cell line RAW 264.7 with thapsigargin, an endomembrane Ca(2+)-ATPase inhibitor, induced histamine production in a time- and concentration-dependent manner. 2. The protein kinase C activator, 12-O-tetradecanoylphorbol 13-acetate (TPA), also enhanced histamine production. 3. alpha...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0703085
更新日期：2000-02-01 00:00:00
abstract：:1 Vasoactive intestinal polypeptide (VIP, 0.01- MicroM) produced dose-related relaxations of the mouse anococcygeus muscle. 2 Following incubation with indomethacin (2.8 microM 1 h) adenosine 5'-triphosphate (ATP, 0.5-10 mM) produced dose-related relaxations of the mouse anococcygeus. 3 Haemolysed blood reduced inhibi...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1982.tb09274.x
更新日期：1982-09-01 00:00:00
abstract：:1. Enprostil is composed, in approximately equal proportions, of 4 allenic isomers which are prostanoids structurally related to prostaglandin E2 (PGE2). The isomers are denoted as RS-86505-007, RS-86812-007 which are in the 'natural' R and S configuration (with respect to PGE2) and RS-86505-008 and RS-86812-008 which...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1989.tb12682.x
更新日期：1989-12-01 00:00:00
abstract：:1. Mice pretreated intraperitoneally for 2 days with delta-9-tetrahydrocannabinol (delta-9-THC) at a dose of 20 mg kg-1 day-1 and then challenged intravenously with this drug, 24 h after the second pretreatment, showed a 6 fold tolerance to the hypothermic effect of delta-9-THC. This pretreatment also induced toleranc...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1993.tb13989.x
更新日期：1993-12-01 00:00:00
abstract：BACKGROUND AND PURPOSE:It is well known that adenine-based purines exert multiple effects on pain transmission. However, less attention has been given to the potential effects of guanine-based purines on pain transmission. The aim of this study was to investigate the effects of intraperitoneal (i.p.) and oral (p.o.) ad...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2009.00597.x
更新日期：2010-03-01 00:00:00
abstract：:1. Isolated tissues of the guinea-pig were bathed with Krebs solution at 37 degrees C and subjected to 100 ms pulses of electrical stimulation for 30 min at a frequency of 0.1 or 1.0 Hz. The tissues were then dried, ashed, and the ash analysed for calcium, sodium, potassium and magnesium.2. Gastric smooth muscle, card...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1972.tb08124.x
更新日期：1972-08-01 00:00:00
abstract：:1. In the present study the effect of N-methyl-D-aspartate (NMDA) on thromboxane B2 synthesis and on [Ca2+]i was studied in human platelets. 2. NMDA (10(-7) M) completely inhibited the synthesis of thromboxane B2 from exogenous arachidonic acid (AA), while it did not interfere with the aggregating effect of the thromb...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701790
更新日期：1998-05-01 00:00:00
abstract：BACKGROUND AND PURPOSE:ARL 67156, 6-N,N-Diethyl-D-beta-gamma-dibromomethylene adenosine triphosphate, originally named FPL 67156, is the only commercially available inhibitor of ecto-ATPases. Since the first report on this molecule, various ectonucleotidases responsible for the hydrolysis of ATP at the cell surface hav...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0707361
更新日期：2007-09-01 00:00:00
abstract：:The aims of this study were to develop a technique to measure blood flow in the mouse ear and to investigate the nature of the vasodilator mediator(s) involved in the response to capsaicin. The response to capsaicin, applied topically, was investigated in anaesthetized CD1 or Sv129+C57BL/6 wild-type (+/+) or NK(1) rec...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0704485
更新日期：2002-01-01 00:00:00
abstract：BACKGROUND AND PURPOSE:(R,S)-ketamine produces rapid and significant antidepressant effects in approximately 65% of patients suffering from treatment-resistant bipolar depression (BD). The genetic, pharmacological and biochemical differences between ketamine responders and non-responders have not been identified. The p...
journal_title：British journal of pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1111/bph.12494
更新日期：2014-04-01 00:00:00
abstract：:1. Effects of an orally active non-peptide (BK) B2 receptor antagonist, FR173657 ((E)-3-(6-acetamido-3-pyridyl)-N-[N-[2,4-dichloro-3-[(2-methyl-8-quinoli nyl) oxymethyl]phenyl]-N-methylaminocarbonylmethyl] acrylamide) on the plasma exudation in rat carrageenin-induced pleurisy were investigated. 2. Plasma exudation in...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701194
更新日期：1997-06-01 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 Isolated duodenum of the rat, exposed to ultraviolet (u.v.) light in the presence of NO2 ions, responded with reversible relaxation. 2 The photorelaxation response did not seem to involve any known receptor mechanisms and was independent of any ganglionic or neuronal influences. 3 Changes in the ionic environment of...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1979.tb13665.x
更新日期：1979-06-01 00:00:00
abstract：:1 Administration of isoprenaline by aerosol inhalation to man results in over 80% being metabolized to the sulphate conjugate.2 The majority of an inhaled dose is probably swallowed since the metabolic pattern resembles that after an oral dose.3 Isoprenaline, administered in aqueous solution directly into the bronchia...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1974.tb08593.x
更新日期：1974-04-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Inhibitory junction potentials (IJP) are responsible for smooth muscle relaxation in the gastrointestinal tract. The aim of this study was to pharmacologically characterize the neurotransmitters [nitric oxide (NO) and adenosine triphosphate (ATP)] and receptors involved at the inhibitory neuromus...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2009.00454.x
更新日期：2009-11-01 00:00:00
abstract：:1. Prolongation of action potentials by cooling or pharmacological treatment can restore conduction in demyelinated axons. We have assessed the ability of pyrethroids (in vitro) to modify action potential kinetics and to reverse conduction block in lesioned peripheral nerve. 2. Fast Na+ currents were isolated in mamma...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701644
更新日期：1998-02-01 00:00:00
abstract：:5-Hydroxytryptamine (5-HT, 5-160 microgram kg-1) injected intravenously in pentobarbitone-anaesthetized, open-chest cats caused dose-dependent increases in pulmonary arterial and intratracheal pressures. There was also a marked systemic hypotension and bradycardia. The pulmonary effects were completely prevented by ke...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1983.tb10033.x
更新日期：1983-10-01 00:00:00
abstract：:1. Impairment of nitric oxide (NO)/cyclic GMP production and/or increased activities of thromboxane A2 (TXA2) and endothelin-1 (ET-1) have been associated with pulmonary hypertension. We have analysed the interactions of noradrenaline (NA), the TXA2-mimetic U46619 and ET-1 with the relaxation induced via cyclic GMP in...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701257
更新日期：1997-08-01 00:00:00
