Abstract:
:1. The present study was designed to evaluate the nature of intervening agents in L-DOPA- and dopamine-induced neurotoxicity in Neuro-2A cells. 2. In the absence of cells and in conditions of light protection, at 37 degrees C, L-DOPA or dopamine (1 mM) in culture medium degraded spontaneously in a time-dependent manner, this being prevented by ascorbic acid (200 microM) and other antioxidants, namely glutathione (1 mM), N-acetyl-L-cysteine (1 mM), sodium metabisulphite (200 microM), but not N-ter-butyl-alpha-phenylnitrone (1 mM) and deferoxamine (100 microM). 3. The viability of Neuro-2A cells declined following treatment with L-DOPA or dopamine in a concentration- and time-dependent manner. The decrease in cell viability by L-DOPA (10+/-4% of control) or dopamine (15+/-4% of control) was markedly attenuated by antioxidants (ascorbic acid, glutathione, N-acetyl-L-cysteine and sodium metabisulphite). Autoxidation of L-DOPA or dopamine was accompanied by the formation of H(2)O(2) in a time-dependent manner, this being completely prevented by ascorbic acid at 24 h or markedly reduced at 48 h. 4. Protective effects of 100 U ml(-1) catalase (40+/-1% of control) against L-DOPA-induced cell death were lower than those conferred by 200 microM ascorbic acid (70+/-3% of control). Catalase-induced protection (59+/-5% of control) against dopamine-induced cell death was similar to that conferred by 200 microM ascorbic acid (57+/-4% of control). L-DOPA-induced neuronal cell death was also accompanied by increases in caspase-3 activity, this being insensitive to ascorbic acid. Dopamine-induced increase in caspase-3 activity occurred only when autoxidation of the amine was prevented by ascorbic acid. 5. It is suggested that in addition to generation of H(2)O(2) and quinone formation, L-DOPA- and dopamine-induced cell death may result from induction of apoptosis, as evidenced by increases in caspase-3 activity. Dopamine per se induces apoptosis by a mechanism independent of oxidative stress, as evidenced by the fact that increases in caspase-3 activity occurred only when autoxidation of the amine was prevented.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Pedrosa R,Soares-da-Silva Pdoi
10.1038/sj.bjp.0704982subject
Has Abstractpub_date
2002-12-01 00:00:00pages
1305-13issue
8eissn
0007-1188issn
1476-5381journal_volume
137pub_type
杂志文章abstract::Gut inflammation occurring in patients with inflammatory bowel diseases (IBD) is associated with an excessive immune response that is directed against constituents of the normal bacterial flora and results in the production of large amounts of inflammatory cytokines. Anti-cytokine compounds, such as the neutralizing T...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1476-5381.2011.01614.x
更新日期:2012-02-01 00:00:00
abstract::1. The effects of nipradilol, a beta-adrenoceptor antagonist which possesses a nitroxy group, on cytosolic Ca2+ concentration ([Ca2+]i), and on tension development were simultaneously measured by front-surface fluorometry and fura-2-loaded strips in the proximal portion of pig coronary arteries. 2. Nipradilol reduced ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb15343.x
更新日期:1996-04-01 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::1 A simple double-isotope assay for phospholipase A2 activity of perfused organs is described; Guinea-pig lungs perfused through the pulmonary circulation exhibit a low background enzyme activity. This activity is blocked by dexamethasone, betamethasone and hydrocortisone, mepacrine, procaine or chlorpromazine. Aspiri...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1978.tb07009.x
更新日期:1978-01-01 00:00:00
abstract::In recent years, late-stage clinical drug development that primarily focuses on urogenital targets has centered around four areas of medical need (both unmet need and aiming to improve on existing therapies). These include male sexual dysfunction (MSD), female sexual dysfunction (FSD), prostatic pathology (neoplastic,...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1038/sj.bjp.0706638
更新日期:2006-02-01 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::It has been hypothesized that in patients with benign prostatic hyperplasia, selective antagonism of the alpha1A-adrenoceptor-mediated contraction of lower urinary tract tissues may, via a selective relief of outlet obstruction, lead to an improvement in symptoms. The present study describes the alpha1-adrenoceptor (a...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702541
更新日期:1999-05-01 00:00:00
abstract::1. Electroconvulsive treatment (ECT) of rabbits produced ocular inflammation consisting of conjunctival hyperaemia, miosis and protein extravasation into the aqueous humour, reflected by the so-called aqueous flare response (AFR): the maximal reduction in pupil size was 3.8 +/- 0.1 mm (s.e. of mean, n = 16) while the ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701083
更新日期:1997-04-01 00:00:00
abstract:BACKGROUND AND PURPOSE:The thiazolidine carboxylic acid, BML-241, has been proposed as a lead compound in development of selective antagonists at the sphingosine-1-phosphate receptor (S1P3), based on its inhibition of the rise in intracellular calcium concentrations ([Ca2+]i) in HeLa cells overexpressing S1P receptors....
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0706872
更新日期:2006-10-01 00:00:00
abstract::1. Membranes from rat cerebral cortex, myocardium and extraorbital lacrimal gland were used as sources of M1, M2 and M3 muscarinic acetylcholine receptors respectively and the affinities of seven antagonists for the three subtypes were examined under different experimental conditions. 2. The affinities for the membran...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1991.tb09827.x
更新日期:1991-06-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Recent findings suggest that the noxious gas H(2)S is produced endogenously, and that physiological concentrations of H(2)S are able to modulate pain and inflammation in rodents. This study was undertaken to evaluate the ability of endogenous and exogenous H(2)S to modulate carrageenan-induced sy...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2010.00640.x
更新日期:2010-04-01 00:00:00
abstract::Three genes encode the small-conductance Ca(2+)-activated K(+) channels (SK channels). We have stably expressed hSK1 and rSK2 in HEK 293 cells and addressed the pharmacology of these subtypes using whole-cell patch clamp recordings. The bee venom peptide apamin blocked hSK1 as well as rSK2 with IC(50) values of 3.3 nM...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703120
更新日期:2000-03-01 00:00:00
abstract::Noradrenaline (NA) and adrenaline (Ad) are modulators of cytokine production. Here we investigated the role of these neurotransmitters in the regulation of macrophage inflammatory protein (MIP)-1alpha expression. Pretreatment of RAW 264.7 macrophages with NA or Ad decreased, in a concentration-dependent manner (1 nM-1...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702179
更新日期:1998-11-01 00:00:00
abstract::1. The effect of the novel ET(A) receptor antagonist LBL 031 and other selective and mixed endothelin receptor antagonists on endothelin-1 (ET-1)-induced and lipopolysaccharide (LPS)-induced microvascular leakage was assessed in rat airways. 2. Intravenously administered ET-1 (1 nmole kg(-1)) or LPS (30 mg kg(-1)) cau...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703691
更新日期:2000-11-01 00:00:00
abstract::1. The aim of this study was to determine the response of porcine small pulmonary arteries to intralumenal flow and to identify the cellular mechanisms and potential mediators involved in the response. 2. Porcine small pulmonary arteries were isolated from a branch of the main intrapulmonary artery of the lower lung l...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701846
更新日期:1998-05-01 00:00:00
abstract:BACKGROUND AND PURPOSE:The present study investigated whether the pathophysiological changes induced by burn and smoke inhalation are modulated by parenteral administration of Na(2)S, a H(2)S donor. EXPERIMENTAL APPROACH:The study used a total of 16 chronically instrumented, adult female sheep. Na(2)S was administered...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2009.00411.x
更新日期:2009-11-01 00:00:00
abstract::1. The effect of intravenous administration of dexamphetamine [+)-Amp) on rat pupil diameter was investigated. In all experiments, the vagosympathetic trunks were sectioned bilaterally at the cervical level. 2. In rats anaesthetized with urethane, (+)-Amp (0.1-0.3 mg kg-1, i.v.) produced a dose-related increase in pup...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1989.tb11781.x
更新日期:1989-01-01 00:00:00
abstract::1. The influence of angiotensin II (AII) on resting blood pressure and on sympathetic nerve-mediated pressor responses in the pithed rat was investigated either by inhibiting the renin-angiotensin system or by infusing AII. 2. Plasma AII levels in the pithed rat were approximately 20 fold higher than in normotensive r...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1988.tb11759.x
更新日期:1988-12-01 00:00:00
abstract::The effects of intravenous doses of Org 6001 and disopyramide (10 mg/kg) known to confer protection against early postligation-induced arrhythmias in the anaesthetized rat when given prophylactically, were assessed following postligation administration. When given 1 min after ligation both drugs greatly reduced the in...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1982.tb09245.x
更新日期:1982-08-01 00:00:00
abstract::1. We have compared the effects of ouabain on the maintenance of gap junctional communication in rat aortic A7r5 smooth muscle cells, monkey COS-1 fibroblasts and human HeLa epithelial cells. 2. Ouabain (1 mM) interrupted dye coupling between confluent A7r5 cells within approximately 1 h, and high concentrations of ou...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705556
更新日期:2003-12-01 00:00:00
abstract::1. In vivo microdialysis has been used to investigate the concentration of various amino acids and lactate in the extracellular fluid of the rat cortex following focal ischaemia, the probe being placed in the core of the infarct area. 2. An ischaemic infarct was produced in the cortex by use of a photochemical dye (Ro...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1994.tb13050.x
更新日期:1994-05-01 00:00:00
abstract::1 The ability of drugs to inhibit noradrenaline accumulation and to release noradrenaline was studied in the isolated anococcygeus muscle of the rat. 2 Noradrenaline, tyramine, 2-amino,6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (ADTN), 2-amino,6,7-dimethoxy-1,2,3,4-tetrahydronaphthalene (dimethyl ADTN), and 5-hydroxy...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1978.tb07798.x
更新日期:1978-07-01 00:00:00
abstract::1. The purpose of the present study was to develop an experimental strategy for the quantification of the cardiovascular effects of non-selective adenosine receptor ligands at the adenosine A1 and A2a receptor in vivo. 2-Chloroadenosine (CADO) was used as a model compound. 2. Three groups of normotensive conscious rat...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb15412.x
更新日期:1996-05-01 00:00:00
abstract::1. Involvement of cholinergic mechanisms in the contractile response to Leu13-motilin (LMT, KW-5139) was investigated in rabbit duodenal segments, and longitudinal muscle-myenteric plexus (LM-MP) preparations preincubated wtih [3H]-choline. 2. Contractile response to LMT (0.1 nM-1 microM) consisted of an initial rapid...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1993.tb13536.x
更新日期:1993-05-01 00:00:00
abstract::1. The calcium sensitivity of force production of cardiac muscle fibres is altered by certain drugs. The sites of action of three such compounds (pimobendan, sulmazole, isomazole) within the myofibril have been investigated. Calmodulin antagonists, perhexilene and bepridil, which have been shown to alter the calcium d...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1990.tb14092.x
更新日期:1990-08-01 00:00:00
abstract::1. We compared the relaxant effect of pituitary adenylate cyclase activating peptide (PACAP) 1-27 with that of a newly developed PACAP 1-27 analogue, [Arg15,20,21Leu17]-PACAP-Gly-Lys-Arg-NH2, in the guinea-pig trachea and primate bronchi in vitro (n = 4-5). 2. In the guinea-pig trachea precontracted by a submaximally ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701310
更新日期:1997-08-01 00:00:00
abstract::The effects of 15-hydroperoxy metabolites of arachidonic acid on vascular tone were evaluated in the perfused mesenteric preparation, the isolated perfused lung and segments of pulmonary arteries of the rat. In the mesenteric preparation, precontracted with phenylephrine, both 15-hydroperoxy-5,8,11,13-eicosatetraenoic...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1987.tb11256.x
更新日期:1987-07-01 00:00:00
abstract::1. Effects of KC399, an opener of ATP-sensitive K+ channels were investigated on membrane potential, isometric force and intracellular Ca2+ ([Ca2+]i) mobilization induced by acetylcholine (ACh) in smooth muscle from the rabbit trachea. 2. In these smooth muscle cells, ACh (0.1 and 1 microM) depolarized the membrane in...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb16642.x
更新日期:1995-08-01 00:00:00
abstract::1. Peroxisome proliferator-activated receptor alpha (PPARalpha) regulates the expression of the key genes involved in lipid metabolism following activation of this receptor by various ligands. Ginseng, a highly valuable medicine in oriental societies, is also reported to modulate lipid metabolism, although the mechani...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705169
更新日期:2003-04-01 00:00:00
abstract:BACKGROUND AND PURPOSE:There is increasing evidence that potassium channels are involved in the cardiovascular dysfunction of sepsis. This evidence was obtained after the systemic inflammation, cardiovascular dysfunction and organ damage had developed. Here we have studied the consequences of early interference with po...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2011.01324.x
更新日期:2011-07-01 00:00:00