Abstract:
:1. We have previously found that human chymase cleaves big endothelins (ETs) at the Tyr31-Gly32 bond and produces 31-amino acid ETs (1-31), without any further degradation products. In this study, we investigated the effect of synthetic ET-1 (1-31) on the proliferation of cultured human coronary artery smooth muscle cells (HCASMCs). 2. ET-1 (1-31) increased [3H]-thymidine incorporation and cell numbers to a similar extent as ET-1 at 100 nM. This ET-1 (1-31)-induced [3H]-thymidine uptake was not affected by phosphoramidon, an inhibitor of ET-converting enzyme. It was, however, inhibited by BQ123, an endothelin ET(A) receptor antagonist, but not by BQ788, an endothelin ET(B) receptor antagonist. 3. By using an in-gel kinase assay, we demonstrated that ET-1 (1-31) activated extracellular signal-regulated kinase 1/2 (ERK1/2) in a concentration-dependent manner (100 pM to 1 microM) in HCASMCs. ET-1 (1-31)-induced ERK1/2 activation was inhibited by BQ123, but not by BQ788 and phosphoramidon. Inhibition of protein kinase C (PKC) and ERK kinase also caused a reduction of ET-1 (1-31)-induced ERK1/2 activation, whereas tyrosine kinase inhibition had little effect. 4. Gel-mobility shift analysis revealed that the ERK1/2 activation was followed by an increase in transcription factor activator protein-1 DNA binding activity in HCASMCs. 5. Our results strongly suggest that ET-1 (1-31) itself stimulates HCASMC proliferation probably through endothelin ET(A) or ET(A)-like receptors. The underlining mechanism of cell growth by ET-1 (1-31) may be explained in part by PKC-dependent ERK1/2 activation. Since human chymase has been proposed to play a role in atherosclerosis, ET-1 (1-31) may be one of the mediators.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Yoshizumi M,Kim S,Kagami S,Hamaguchi A,Tsuchiya K,Houchi H,Iwao H,Kido H,Tamaki Tdoi
10.1038/sj.bjp.0702141subject
Has Abstractpub_date
1998-11-01 00:00:00pages
1019-27issue
5eissn
0007-1188issn
1476-5381journal_volume
125pub_type
杂志文章abstract::After many years of effort, recent technical breakthroughs have enabled the X-ray crystal structures of three G-protein-coupled receptors (GPCRs) (beta1 and beta2 adrenergic and adenosine A(2a)) to be solved in addition to rhodopsin. GPCRs, like other membrane proteins, have lagged behind soluble drug targets such as ...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1476-5381.2009.00476.x
更新日期:2010-03-01 00:00:00
abstract::Rat vas deferens preparations became desensitized to the alpha 1-adrenoceptor antagonist thymoxamine: after 6 h in vitro, the t 1/2 value (time to attain half the occupancy of receptors occupied at equilibrium) of the response to this drug was 1.50 fold greater in control strips (strips exposed to thymoxamine at 6 h) ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1984.tb10113.x
更新日期:1984-09-01 00:00:00
abstract::In circular smooth muscle cells of the guinea-pig stomach (antrum), diltiazem (10(-6)-10(-5)M) blocked the overshooting spike potential generated either spontaneously or by electrical stimulation in the presence of 2 mM tetraethylammonium chloride, but did not block the slow wave and the abortive spike potential. The ...
journal_title:British journal of pharmacology
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doi:10.1111/j.1476-5381.1985.tb11100.x
更新日期:1985-12-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Atrial fibrillation (AF) is the most common electrical cardiac disorder in clinical practice. The major trigger for AF is focal ectopic activity of unknown origin in sleeves of cardiac muscle that extend into the pulmonary veins. We examined the role of noradrenaline in the genesis of ectopic act...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0707177
更新日期:2007-04-01 00:00:00
abstract::1. The effects of 2-amino-5-phosphonovalerate and kynurenate, either alone or in combination, were tested on responses evoked by the excitatory amino acid agonists quinolinate, ibotenate, N-methyl-D-aspartate and N-methyl-DL-aspartate by use of an in vitro preparation of mouse neocortex and artificial cerebrospinal fl...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1988.tb10328.x
更新日期:1988-03-01 00:00:00
abstract::The endothelial 5-HT receptor mediating relaxation of pig pulmonary artery has been characterized using the selective 5-HT(2B) receptor agonist BW 723C86 and a variety of structurally diverse 5-HT receptor antagonists. If arterial rings with intact endothelium were precontracted with prostaglandin F(2alpha) (3 microM)...
journal_title:British journal of pharmacology
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doi:10.1038/sj.bjp.0703341
更新日期:2000-06-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1989.tb12601.x
更新日期:1989-10-01 00:00:00
abstract::1 Atrial pacing at progressively increasing frequencies was performed on unanaesthetized dogs through electrodes placed aseptically in the wall of the right atrium and exteriorized in the neck region. 2 Heart rate and two atrioventricular conduction (AVC) parameters, namely the Wenckebach Point (one or two systole blo...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1982.tb09300.x
更新日期:1982-10-01 00:00:00
abstract::The binding of a series of amide derivatives of methotrexate to Lactobacillus casei dihydrofolate reductase has been studied by inhibition constant measurements and by 1H n.m.r. spectroscopy. Amide modification of the alpha-carboxylate of methotrexate was found to prevent interaction of the gamma-carboxylate with the ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1984.tb10080.x
更新日期:1984-02-01 00:00:00
abstract::1. The effects of sulphone have been studied on kinin production in dog plasma and on capillary permeability in the skin of rabbits.2. Dog plasma was used as a substrate for pancreatic kallikrein in vitro and the addition of sulphone caused an inhibition of kinin production, which was dependent on the concentration of...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1969.tb09534.x
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abstract::1. Primary porcine hepatocytes and enterocytes were isolated and cultured in Williams' E medium for up to 10 days to investigate potential organ differences in the metabolism of the immunosuppressive compound tacrolimus (FK 506) and of two investigational drugs (KC11346 and KC12291). Using LC-MS (FK506) and HPLC-FL (K...
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doi:10.1038/sj.bjp.0703062
更新日期:2000-01-01 00:00:00
abstract:BACKGROUND AND PURPOSE:A functional link between seizure-induced P-glycoprotein overexpression at the blood-brain barrier and therapeutic failure has been suggested by several studies using rodent epilepsy models and human epileptic tissue. Recently, we reported that interference with the mechanisms that up-regulate P-...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2010.00765.x
更新日期:2010-07-01 00:00:00
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更新日期:2015-07-01 00:00:00
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pub_type: 杂志文章
doi:10.1038/sj.bjp.0707221
更新日期:2007-05-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703826
更新日期:2001-01-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1038/sj.bjp.0707490
更新日期:2008-03-01 00:00:00
abstract::1. The pharmacological characteristics of RP 67580, a non-peptide tachykinin NK1 receptor antagonist, and its effects on a reflex response evoked by stimulation of primary afferent fibres, were examined in isolated neonatal spinal cord preparations of the rat. Potentials were recorded extracellularly from a lumbar ven...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1994.tb17116.x
更新日期:1994-12-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2011.01794.x
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1971.tb08035.x
更新日期:1971-02-01 00:00:00
abstract::1. Tyramine 10(-4)M significantly increased release of noradrenaline-7-(3)H (NA-7-(3)H) from rat vas deferens in vitro.2. Neither cocaine 10(-5)M nor imipramine 10(-7)M-10(-6)M significantly reduced tyramine-induced release of NA-7-(3)H.3. Increasing the exposure time to cocaine and imipramine from 10 to 20 min or pre...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1969.tb08305.x
更新日期:1969-05-01 00:00:00
abstract::Inhibition of myocardial Ca2+ channels was investigated for three dihydropyridines with different structural features: Ro 18-3981, darodipine (PY 108-068) and nifedipine. Ro 18-3981 contains a sulphamoyl acetyl side-chain. In voltage-clamps experiments with isolated cardiac myocytes of guinea-pig, Ro 18-3981 caused a ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1987.tb08983.x
更新日期:1987-05-01 00:00:00
abstract::1. The effect of mastoparan on phosphatidylcholine hydrolysis was examined in 1321N1 human astrocytoma cells. Mastoparan (3-30 microM) caused an accumulation of diacylglycerol (DG) and phosphatidic acd (PA) accompanied by choline release in a concentration- and time-dependent manner. 2. In the presence of 2% n-butanol...
journal_title:British journal of pharmacology
pub_type: 杂志文章
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1983.tb10031.x
更新日期:1983-10-01 00:00:00
abstract::1. This study describes attempts to compare prostacyclin (IP-) receptors in human, pig, horse, rabbit and rat platelets and in circular muscle of human, rabbit and dog mesenteric and pig gastroepiploic arteries. Three stable prostacyclin analogues, iloprost, cicaprost and 6a-carba-prostacyclin (6a-carba-PGI2) and a pr...
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pub_type: 杂志文章
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更新日期:1989-07-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703451
更新日期:2000-08-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1993.tb13972.x
更新日期:1993-12-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1981.tb10471.x
更新日期:1981-11-01 00:00:00
abstract::1. The potassium-sparing diuretic, amiloride, has been shown to inhibit the Na/Ca exchange system in various preparations. The effects of this drug have been investigated on the contractions of guinea-pig aortic strips elicited by reduction of external K, by addition of ouabain and by removal of external Na. 2. Amilor...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1988.tb10316.x
更新日期:1988-03-01 00:00:00
abstract::The smooth muscle relaxant responses to the mixed beta(3)-, putative beta(4)-adrenoceptor agonist, (-)-CGP 12177 in rat colon are partially resistant to blockade by the beta(3)-adrenoceptor antagonist SR59230A suggesting involvement of beta(3)- and putative beta(4)-adrenoceptors. We now investigated the function of th...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703365
更新日期:2000-06-01 00:00:00