Abstract:
:1 Endothelin-1 (ET-1), an endothelium-derived vasoactive peptide, participates in the regulation of endothelial function through mechanisms that are not fully elucidated. This study examined the impact of ET-1 on oxidative stress, apoptosis and cell proliferation in human umbilical vein endothelial cells (HUVEC). HUVECs were challenged for 24 h with ET-1 (10 pM-10 nM) in the absence or presence of the ET(B) receptor antagonist BQ788 (1 microM) or the NADPH oxidase inhibitor apocynin (1 microM). Reactive oxygen species (ROS) were detected using chloromethyl-2',7'-dichlorodihydrofluorescein diacetate. Apoptosis was evaluated with 4',6'-diamidino-2'-phenylindoladihydrochloride staining and by the caspase-3 assay. Cell proliferation was measured by a colorimetric assay. Expression of NADPH oxidase, Akt, pAkt, Bcl-2, Bax, IkappaB, caveolin-1 and eNOS was evaluated by Western blot analysis. 2 ET-1 significantly enhanced ROS generation and cell proliferation following 24-h incubation, both of which were prevented by BQ788 or apocynin, consistent with the ability of ET-1 to directly upregulate NADPH oxidase. ET-1 itself did not affect apoptosis but attenuated homocysteine-induced apoptosis through an ET(B) receptor-mediated mechanism. Western blot analysis indicated that ET-1 alleviated homocysteine (Hcy)-induced apoptosis, likely acting by antagonizing the Hcy-induced decreases in Akt, pAkt, pAkt-to-Akt, Bcl-2-to-Bax ratios and increases in Bax and caveolin-1 expression. Furthermore, ET-1 downregulated expression of caveolin-1 and eNOS, which was attenuated by BQ788 or apocynin. 3 In summary, our results suggest that ET-1 affects oxidative stress, proliferation and apoptosis possibly through ET(B), NADPH oxidase, Akt, Bax and caveolin-1-mediated mechanisms.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Dong F,Zhang X,Wold LE,Ren Q,Zhang Z,Ren Jdoi
10.1038/sj.bjp.0706193subject
Has Abstractpub_date
2005-06-01 00:00:00pages
323-33issue
3eissn
0007-1188issn
1476-5381pii
0706193journal_volume
145pub_type
杂志文章abstract::Adrenergic transmission was investigated in the dog mesenteric vein by recording electrical responses of single smooth muscle cells to perivascular nerve stimulation. Perivascular nerve stimulation generated an excitatory junction potential (e.j.p.) and a slow depolarization of the membrane. The amplitude of the e.j.p...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1984.tb10101.x
更新日期:1984-03-01 00:00:00
abstract::We investigated the ability of the cannabinoid agonists CP55,940 (CB(1)/CB(2)) and anandamide (endogenous cannabinoid) to modulate electrical field stimulation (EFS)-induced acetylcholine (ACh) release from parasympathetic nerve terminals innervating guinea-pig trachea. We assessed whether modulation of transmitter re...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703497
更新日期:2000-08-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Hydrogen sulphide (H(2)S) is a labile, endogenous metabolite of cysteine, with multiple biological roles. The development of sulphide-based therapies for human diseases will benefit from a reliable method of quantifying H(2)S in blood and tissues. EXPERIMENTAL APPROACH:Concentrations of reactive...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2010.00704.x
更新日期:2010-06-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Rho kinase (ROCK) activation is involved in neuroinflammatory processes leading to progression of neurodegenerative diseases such as Parkinson's disease. Furthermore, ROCK plays a major role in angiogenesis. Neuroinflammation and angiogenesis are mechanisms involved in developing l-DOPA-induced d...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.15275
更新日期:2020-12-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Voltage-operated sodium channels constitute major target sites for local anaesthetic-like action. The clinical use of local anaesthetics is still limited by severe side effects, in particular, arrhythmias and convulsions. These side effects render the search for new local anaesthetics a matter of...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/bjp.2008.255
更新日期:2008-09-01 00:00:00
abstract::1. Nine non-steroidal anti-inflammatory drugs were tested for antagonism of bradykinin-induced bronchoconstriction in guinea-pig lungs in vivo. Only one, benzydamine, was inactive.2. The descending order of potency of the active anti-inflammatory drugs was meclofenamate = Scha 306>Scha 87/2>indoxole>Mi85>indomethacin>...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1968.tb07952.x
更新日期:1968-09-01 00:00:00
abstract::Heart disease is a major cause of morbidity and mortality throughout the world. Some cardiovascular conditions can be modulated by lifestyle factors such as increased exercise or a healthier diet, but many require surgical or pharmacological interventions for their management. More targeted and less invasive therapies...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bph.13678
更新日期:2017-10-01 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 isolated basilar artery of the rabbit, gamma-aminobutyrate acid (GABA) (ED50 +/- s.e. mean, 2.4 +/- 1.1 x 10(-5) M) produced a relaxation, if the tone had been increased with 5-hydroxytryptamine (5-HT). 2 3-Aminoproprane sulphonic acid (3-APS) produced a similar, but smaller relaxation, while baclofen had no ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1982.tb08770.x
更新日期:1982-01-01 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::1. The psychoactive cannabinoids (-)-delta 9-tetrahydrocannabinol ((-)-delta 9-THC) and the 1,1-dimethyl-heptyl homologue of (-)-11-hydroxy-delta 8-tetrahydrocannabinol ((-)-DMH) both inhibited electrically-evoked contractions of the mouse isolated vas deferens and the myenteric plexus-longitudinal muscle preparation ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1992.tb09088.x
更新日期:1992-04-01 00:00:00
abstract::1. The ability of the neuroprotective agent, lifarizine (RS-87476), to mitigate veratridine-, cyanide- and glutamate-induced toxicity in rat embryonic cerebrocortical neurones in primary culture has been compared with that of tetrodotoxin (TTX), nitrendipine, (+)-MK-801 and (-)-MK-801. Lactate dehydrogenase (LDH) rele...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb13357.x
更新日期:1995-04-01 00:00:00
abstract::1. The effects of alpha 2-adrenoceptor and kappa-opiate receptor activation on 45Ca accumulation into rat cortical synaptosomes were examined. 2. Clonidine (1 microM) and U50488H (1 microM) significantly reduced 45Ca accumulation under both resting (5 mM K+) and depolarizing (15-30 mM K+) conditions. 3. The inhibitory...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1990.tb12103.x
更新日期:1990-09-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Angiotensin II (AngII) induces migration and growth of vascular smooth muscle cell (VSMC), which is responsible for vascular remodelling in some cardiovascular diseases. Ang II also activates a Cl(-) current, but the underlying mechanism is not clear. EXPERIMENTAL APPROACH:The A10 cell line and ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.13385
更新日期:2016-02-01 00:00:00
abstract::1. The effects of some rapidly metabolized sympathomimetic amines, such as beta-phenylethylamine and p-tyramine, in eliciting hypertensive responses to reserpine in the anaesthetized rat, have been studied.2. Retardation of metabolism, by pretreatment with the monoamineoxidase inhibitors iproniazid or phenelzine, caus...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1972.tb07256.x
更新日期:1972-02-01 00:00:00
abstract::1. The aim of the present experiments was to determine whether 5-HT1A receptors play a role in the control of the reflex activation of pulmonary vagal motoneurones. This was carried out by investigating the effects of intracisternal injections (i.c.) of the 5-HT1A receptor ligands, 8-OH-DPAT (50 micrograms kg-1), busp...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb15250.x
更新日期:1996-02-01 00:00:00
abstract::The concentration-dependence of the negative and positive inotropic effect of choline esters and of oxotremorine was studied in isometrically contracting papillary muscles of the guinea-pig. The preparations were obtained from reserpine-pretreated animals and were electrically driven at a frequency of 0.2 Hz. In the p...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1987.tb16827.x
更新日期:1987-01-01 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::C-C chemokine receptor-1 (CCR1) has been implicated in mediating a variety of inflammatory conditions including multiple sclerosis and organ rejection. Although originally referred to as the MIP-1alpha/RANTES receptor, CCR1 is quite promiscuous and can be activated by numerous chemokines. We used radioligand binding a...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704907
更新日期:2002-11-01 00:00:00
abstract::1. Dopamine efflux following single pulse or train of pulse stimulations was measured in slices of rat caudate putamen, nucleus accumbens and tuberculum olfactorium, using fast cyclic voltammetry at a carbon fibre microelectrode; 1, 5, 10, 20 or 50 pulses were applied at each location at frequencies varying from 10 Hz...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1992.tb14355.x
更新日期:1992-06-01 00:00:00
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 ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704075
更新日期:2001-06-01 00:00:00
abstract::1. The effect of the nitro-derivative of aspirin, NCX4016, was assessed on ischaemic ventricular arrhythmias and myocardial infarct size in anaesthetized pigs in comparison to native aspirin. 2. Pigs were given aspirin (10 mg kg(-1); n=6), low dose NCX4016 (18.4 mg kg(-1); n=6) or high dose NCX4016 (60 mg kg(-1); n=7)...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704646
更新日期:2002-04-01 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. Prostanoids induce a wide range of biological actions which are mediated by specific membrane-bound receptors. We have recently shown that the E-type prostaglandins, PGE1 and PGE2, effectively inhibit eosinophil aggregation induced by platelet-activating factor (PAF). In an attempt to determine which prostanoid rec...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701107
更新日期:1997-05-01 00:00:00
abstract::1. Immunohistochemical and functional studies have been performed to localize and determine the effects of neuropeptide Y (NPY) in the rat seminal vesicle. 2. An abundant presence of NPY-immunoreactive nerves, mainly concentrated in the smooth muscle layer of the seminal vesicle was found. Chronic 6-hydroxydopamine tr...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1994.tb17074.x
更新日期:1994-11-01 00:00:00
abstract::Until recently, hydrogen sulfide (H2 S) was exclusively viewed a toxic gas and an environmental hazard, with its toxicity primarily attributed to the inhibition of mitochondrial Complex IV, resulting in a shutdown of mitochondrial electron transport and cellular ATP generation. Work over the last decade established mu...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bph.12369
更新日期:2014-04-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Peptide YY (PYY) and neuropeptide Y (NPY) activate Y receptors, targets under consideration as treatments for diarrhoea and other intestinal disorders. We investigated the gastrointestinal consequences of selective PYY or NPY ablation on mucosal ion transport, smooth muscle activity and transit u...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2011.01401.x
更新日期:2011-09-01 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. N-methyl-gamma-aminobutyrate (N-methylGABA), N-methylglycine, N-methyltaurine and N-methylbeta-alanine diminished the frequency of spontaneous spike discharges in guinea-pig cerebellar slices. Usually a weak excitatory effect preceded the inhibition. 2. The inhibitory effects of N-methylGABA and N-methylbeta-alanin...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1977.tb07720.x
更新日期:1977-04-01 00:00:00
abstract::Ouabain was administered at a loading dose of 3 mug/kg followed by an infusion at a rate of 1 mug/kg-1 min-1 in order to produce severe dysrhythmia in dogs within 60 minutes. Similarly, digitoxin at a loading dose of 9 mug/kg followed by an infusion at a rate of 3 mug kg-1 min-1 was administered to compare its effect ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1977.tb06982.x
更新日期:1977-01-01 00:00:00