Abstract:
:We tested the hypothesis that combined use of trophic factors and caspase inhibitors increases brain resistance to ischaemia in mice. Intracerebroventricular administration of bFGF (>10 ng) 30 min after MCA occlusion decreased infarct size and neurological deficit in a dose-dependent manner following 2 h ischemia and reperfusion (20 h). Combined administration of the subthreshold doses of bFGF (3 ng) and caspase inhibitors (z-VAD.FMK, 27 ng or z-DEVD.FMK, 80 mg) reduced infarct volume by 60%, and reduced neurological deficit. Treatment with a subthreshold dose of bFGF (3 ng) extended the therapeutic window for z-DEVD.FMK (480 ng) from 1 to 3 h after reperfusion. Caspase-3 activity in the ischaemic brain was increased 30 min and 2 h after reperfusion but, was significantly reduced in bFGF-treated animals by 29 and 16%, respectively. Caspase-3 activity was not reduced by a direct bFGF effect because addition of bFGF (10 nM - 2 microM) did not decrease recombinant caspase-3 activity, in vitro. Our data show that combining caspase inhibitors and bFGF lengthens the treatment window for the second treatment, plus lowers the dosage requirements for neuroprotection. These findings are important because low doses of caspase inhibitors or bFGF reduce the possibility of side effects plus extend the short treatment window for ischaemic stroke.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Ma J,Qiu J,Hirt L,Dalkara T,Moskowitz MAdoi
10.1038/sj.bjp.0704075subject
Has Abstractpub_date
2001-06-01 00:00:00pages
345-50issue
3eissn
0007-1188issn
1476-5381journal_volume
133pub_type
杂志文章abstract::Growing evidence suggests that interleukin (IL)-13, a Th2-type cytokine, plays a critical role in the development of bronchial hyper-responsiveness (BHR), an essential feature of asthma, although the underlying mechanisms remain unknown. In the present study, we investigated whether IL-13 directly affects airway smoot...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705558
更新日期:2003-12-01 00:00:00
abstract::1. Sympathetic neurotransmission and noradrenaline content of the tail artery of Wistar rats treated for 7 days with the adenosine antagonist, 1,3-dipropyl-8-sulphophenylxanthine (DPSPX), were examined. 2. Systolic blood pressure of the DPSPX-treated rats (164.0 +/- 2.9 mmHg; n = 6) was significantly greater than sali...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb16683.x
更新日期:1995-09-01 00:00:00
abstract::(1) Rapid desensitization of ligand-gated ion channel receptors can alter the apparent activity of receptor modulators, as well as make detection of fast-channel activation difficult. Investigation of the antagonist pharmacology of ATP-sensitive homomeric P2X3 receptors is limited by agonist-evoked fast-desensitizatio...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705411
更新日期:2003-09-01 00:00:00
abstract::1. Noradrenaline sensitivity and acetylcholine-induced relaxation were investigated in mesenteric resistance arteries from female Wistar rats (220-250 g) following exposure to isotonic supraphysiological glucose solutions (20 and 45 mM, in physiological buffer, 2 h incubation). 2. Arteries incubated in 20 mM glucose d...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1994.tb17064.x
更新日期:1994-11-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Although there are many new specific phosphodiesterase inhibitors with anti-inflammatory activity, none have yet reached the market because of their low therapeutic efficacy. Our study was aimed to evaluate the anti-inflammatory and anti-arthritic effect of an established phosphodiesterase inhibi...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2009.00468.x
更新日期:2009-12-01 00:00:00
abstract::1 The effect of thiopentone, methohexitone, urethane and ketamine on the uptake and release of gamma-aminobutyric acid (GABA) and D-aspartate by rat thalamic slices has been investigated. 2 A high, supra-anaesthetic concentration of methohexitone increased the uptake of both D-aspartate and GABA. 3 None of the anaesth...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1982.tb08776.x
更新日期:1982-01-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Neuropeptides are involved in the regulation of food intake in the central nervous system, but they might also act on peripheral fat tissue via neuropeptide receptors. EXPERIMENTAL APPROACH:We investigated the receptor expression and activity of pituitary adenylate cyclase-activating polypeptide...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2009.00164.x
更新日期:2009-06-01 00:00:00
abstract::Following the discovery of the involvement of the ribonucleoprotein TDP-43 in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD), a major research focus has been to develop treatments that can prevent or alleviate these disease conditions. One pharmacological approach has been to use TDP-...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bph.15148
更新日期:2020-05-29 00:00:00
abstract::1. The rat spinal cord in vitro has been used to assess the effect of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) on the dorsal root evoked extracellular ventral root reflex (DR-VRR) and the intracellular excitatory postsynaptic potential (e.p.s.p.) in ventral horn neurones and motoneurones. 2. CNQX (1-5 microM) produ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1992.tb12754.x
更新日期:1992-10-01 00:00:00
abstract::Oxidized low density lipoproteins (oxLDL) are thought to play a major role in atherosclerosis. OxLDL act in part through alteration of intracellular signalling pathways in cells of the vascular wall. We recently reported that the EGF receptor (EGFR) signalling pathway is activated by lipid peroxidation products (among...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703981
更新日期:2001-04-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Mitochondrial aldehyde dehydrogenase (ALDH-2) has been shown to provide a pathway for bioactivation of organic nitrates and to be prone to desensitization in response to highly potent, but not to less potent, nitrates. We therefore sought to support the hypothesis that bioactivation by ALDH-2 cri...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0707116
更新日期:2007-02-01 00:00:00
abstract::1 A range of opioid receptor agonists were tested for activity in five antinociceptive models: the acetylcholine-induced abdominal constriction, tail-flick and hot plate tests in the mouse and the paw pressure test in the rat and guinea-pig. 2 Agonists acting preferentially at the kappa-opioid receptor were significan...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1987.tb11281.x
更新日期:1987-08-01 00:00:00
abstract::1. Gallamine, dequalinium and a novel bis-quaternary cyclophane, UCL 1530 (8,19-diaza-3(1,4),5(1,4)-dibenzena-1 (1,4),7(1,4)-diquinolina-cyclononadecanephanedium) were tested for their ability to block actions mediated by the small conductance, apamin-sensitive Ca(2+)-activated K+ (SKCa) channels in rat cultured sympa...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb15151.x
更新日期:1996-01-01 00:00:00
abstract::1 The effect of local elevation of leucocyte cyclic adenosine 3',5'-monophosphate (cyclic AMP) content on the continued migration of leucocytes to a site of acute inflammation was studied in the pleural cavity of rats. 2 Leucocyte cyclic AMP levels were elevated by injecting with the irritant into the pleural cavity d...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1977.tb07742.x
更新日期:1977-06-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Oxaliplatin is a platinum-based chemotherapeutic drug used as a first-line therapy for colorectal cancer. However, its use is associated with severe gastrointestinal side-effects resulting in dose limitations and/or cessation of treatment. In this study, we tested whether oxidative stress, caused...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.13646
更新日期:2016-12-01 00:00:00
abstract::1. Histamine contracted the tracheal and major bronchial muscles of sheep and relaxed the muscles of the lesser bronchi and bronchioles.2. The stimulant action of histamine on the trachea was antagonized by mepyramine, whereas the relaxant effect on the bronchial tree was not.3. 5-Hydroxytryptamine contracted the musc...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1969.tb07997.x
更新日期:1969-07-01 00:00:00
abstract::For almost three decades intrathecal baclofen therapy has been the standard treatment for spinal cord injury spasticity when oral medication is ineffective or produces serious side effects. Although intrathecal baclofen therapy has a good clinical benefit-risk ratio for spinal spasticity, tolerance and the life-threat...
journal_title:British journal of pharmacology
pub_type: 评论,杂志文章
doi:10.1111/j.1476-5381.2010.00964.x
更新日期:2010-11-01 00:00:00
abstract::Nicotine and dimethyl-phenylpiperazinium (DMPP) increased intravesicular pressure and then transiently depressed the spontaneous activity of the urinary bladder in chloralose anaesthetized cats. Adrenaline (5-10 micrograms kg-1), noradrenaline (5-20 micrograms kg-1) and isoprenaline (40-50 micrograms kg-1) which depre...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1984.tb16494.x
更新日期:1984-10-01 00:00:00
abstract::1. The actions on the taenia of 4-(m-chlorophenylcarbamoyloxy)-2-butynyl-trimethylammonium chloride (McN-A-343), N-benzyl-3-pyrrolidyl acetate methobromide (AHR-602), tetramethylammonium (TMA) and choline phenyl ether have been examined and compared with the actions of acetylcholine, nicotine and 1,1-dimethyl-4-phenyl...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1969.tb08303.x
更新日期:1969-05-01 00:00:00
abstract:BACKGROUND AND PURPOSE:The dietary trace amines tyramine and beta-phenylethylamine (beta-PEA) can increase blood pressure. However, the mechanisms involved in the vascular effect of trace amines have not been fully established. The purpose of this study was to evaluate whether trace amine-dependent vasoconstriction was...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/bjp.2008.286
更新日期:2008-10-01 00:00:00
abstract::The iodine-containing contrast medium iopanoic acid induces alterations of thyroid hormone metabolism comparable to those observed with the iodine-containing antiarrhythmic drug amiodarone. Both compounds inhibit the intracellular conversion of thyroxine (T4) to triiodothyronine (T3). Using iopanoic acid, the question...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1986.tb10217.x
更新日期:1986-06-01 00:00:00
abstract::The arterial endothelium critically contributes to blood pressure control by releasing vasodilating autacoids such as nitric oxide, prostacyclin and a third factor or pathway termed 'endothelium-derived hyperpolarizing factor' (EDHF). The nature of EDHF and EDHF-signalling pathways is not fully understood yet. However...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1476-5381.2009.00132.x
更新日期:2009-06-01 00:00:00
abstract::Knock-out (KO) mouse technology has given pharmacologists a powerful tool to study function in the absence of selective antagonists or inhibitors. Such KO technology can confirm predicted function, serendipitously reveal unrecognized function, or help define the mode of action of a drug. In this issue, Liles et al. de...
journal_title:British journal of pharmacology
pub_type: 评论,杂志文章
doi:10.1038/sj.bjp.0706941
更新日期:2007-01-01 00:00:00
abstract::1. The potencies of some beta-adrenoreceptor blocking drugs in reducing noradrenaline uptake by the isolated heart were compared with their potencies in reducing the release of noradrenaline from the heart by tyramine.2. Of the drugs tested, propranolol, pronethalol and dichloroisoprenaline were the most potent in blo...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1968.tb07957.x
更新日期:1968-09-01 00:00:00
abstract:BACKGROUND AND PURPOSE:5-Hydroxytryptamine (5-HT) has been shown to control and modulate many physiological and behavioural functions in insects. In this study, we report the cloning and pharmacological properties of a 5-HT(1) receptor of an insect model for neurobiology, physiology and pharmacology. EXPERIMENTAL APPR...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2010.00638.x
更新日期:2010-04-01 00:00:00
abstract::1. In Ca-free solution, the contractile response of guinea-pig taenia caecum to 10(-4) M carbachol was mediated through muscarinic receptors and was reduced time-dependently by desensitization with 10(-4) M carbachol, but not 10(-4) M histamine. On the other hand, the response to 10(-4) M histamine was shown to be med...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1988.tb11600.x
更新日期:1988-07-01 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::We have shown earlier that activation of metabotropic glutamate (mGlu) receptors using a group I-specific mGlu receptor agonist, (RS)-3,5-dihydroxyphenylglycine (DHPG), can induce long-term depression (LTD) in the CA1 region of the hippocampus. In an attempt to determine the signal transduction mechanisms involved in ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703905
更新日期:2001-03-01 00:00:00
abstract::1. In the present study, the properties of glaucine (an aporphine structurally related to papaverine) were compared with those of papaverine, diltiazem, nifedipine and prazosin. The work includes functional studies on rat isolated aorta contracted with noradrenaline, caffeine or KCl, and a determination of the affinit...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1992.tb14345.x
更新日期:1992-06-01 00:00:00
abstract::1. The effect of the myorelaxant drugs baclofen, diazepam and tizanidine have been compared on in vitro preparations of baby rat spinal cord and adult rat superior cervical ganglion. 2. Dorsal root-elicited long duration (time to half decay 9.71 +/- 0.29 s.e. mean, n = 31) ipsilateral ventral root reflexes (DR-VRP), m...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1992.tb12794.x
更新日期:1992-10-01 00:00:00