Abstract:
:1 Prolonged exposure (6-12 h) of rat aorta to alpha1-adrenergic receptor (alpha(1)AR) agonist phenylephrine (Phe) leads to a decrease in alpha(1)AR-mediated vasoconstriction. This reduced responsiveness to alpha(1)AR stimulation was strongly dependent on the intactness of the endothelium. 2 We examined the effect of Phe on nitric oxide synthase (NOS) activity by measuring the conversion of [(3)H]L-arginine to [(3)H]L-citrulline in rat aorta or in endothelial cells isolated from rat aorta. Phe stimulation increased NOS activity in control aortas. This response was antagonized by prazosin. However, Phe increased neither the activity of NOS nor intracellular Ca(2+) in the isolated endothelial cells from the control aortas, whereas acetylcholine (Ach) was able to stimulate both responses in these cells. This result suggests that Phe stimulates alpha(1)AR on vascular smooth muscle cells and has an indirect influence on endothelial cells to increase NOS activity. 3 In Phe-exposed aortic rings, basal NOS activity was found to have increased compared to vehicle-exposed control rings. Stimulation with Phe or Ach caused a small increase over basal NOS activity in these preparations. Prolonged exposure to Phe also caused an enhancement of Ach-mediated vasorelaxation in rat aorta. 4 Immunoblot and reverse transcription-polymerase chain reaction experiments showed that prolonged exposure of rat aorta to Phe resulted in an increased expression of eNOS, but not iNOS. This increase was antagonized by nonselective antagonist prazosin. Immunohistochemical staining experiments also showed that expression of eNOS increased in endothelial cells after Phe exposure of the aortas. 5 These results, all together, showed that prolonged exposure of rat aorta to alpha(l)AR agonist Phe enhanced the expression of eNOS and basal NOS activity, which probably causes a decreased vasocontractile response to Phe or to other agonists such as 5HT (5-hydroxytryptamine) in rat aorta. 6 This phenomenon can be considered more as a functional antagonism of vasocontractile response to agonists mediated by endothelium than a specific desensitization of alpha(1)AR-mediated signalling in vascular smooth muscle cells.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Gürdal H,Can A,Uğur Mdoi
10.1038/sj.bjp.0706177subject
Has Abstractpub_date
2005-05-01 00:00:00pages
203-10issue
2eissn
0007-1188issn
1476-5381pii
0706177journal_volume
145pub_type
杂志文章abstract::1 Very highly purified (greater than 100,000 u/mg) slow reacting substance of anaphylaxis (SRS-A) has been prepared by reversed phase high pressure liquid chromatographic (HPLC) techniques. 2 High resolution liquid chromatography suggests that SRS-A may exist in at least three distinct forms which are possible tautome...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1980.tb10696.x
更新日期:1980-01-01 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:BACKGROUND AND PURPOSE:Calu-3 cells are derived from serous cells of human lung submucosal glands, a prime target for therapy in cystic fibrosis (CF). Calu-3 cells can be cultured to form epithelia capable of transepithelial transport of chloride. A CF Calu-3 cell is not available. EXPERIMENTAL APPROACH:A retroviral v...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0707175
更新日期:2007-04-01 00:00:00
abstract::The selective monoamine oxidase (MAO) inhibitors clorgyline, selegiline and AGN 1135 did not cause a change in responses of the cat nictitating membrane to preganglionic sympathetic nerve stimulation at 5 Hz. Both selective MAO-A and MAO-B inhibitors markedly potentiated nictitating membrane contractions in response t...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1985.tb08891.x
更新日期:1985-06-01 00:00:00
abstract::1 Ca(2+)-activated Cl(-) currents (I(Cl(Ca))) evoked by K(+)-free pipette solutions containing 500 nM Ca(2+) were recorded in rabbit pulmonary artery smooth muscle cells. A voltage step protocol in which the cells were stepped to +70 mV and then to -80 mV produced outward and inward Cl(-) currents respectively that ex...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705000
更新日期:2003-01-01 00:00:00
abstract::The kallikrein-kinin system is subdivided into the plasma and tissue-kallikrein-kinin system, with bradykinin (BK) and kallidin (KAL) (Lys(0)-bradykinin) as functional peptides. This occurs in both humans and other mammals. Both peptides are released by plasma and tissue-kallikrein. BK, but not KAL, has been detected ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0706409
更新日期:2005-12-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Catechol-O-methyltransferase (COMT) inhibitors are used in Parkinson's disease in which pain is an important symptom. COMT polymorphisms modulate pain and opioid analgesia in humans. In rats, COMT inhibitors have been shown to be pro-nociceptive in acute pain models, but also to attenuate allodyn...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2010.00999.x
更新日期:2010-12-01 00:00:00
abstract::1. Sigma (sigma) receptors have generated a great deal of interest on the basis of their possible roles in various pathologies, including cytoprotection. Although the exact function of sigma-1 (sigma(1)) receptors is not yet known, their role in the regulation of intracellular Ca(2+) levels and sterol biosynthesis, fu...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704626
更新日期:2002-04-01 00:00:00
abstract::1. Turning behaviour after unilateral lesions of the nigro-striatal dopamine pathway in rats has been used to compare the actions of cocaine and desipramine on central dopamine-containing neurones.2. Administration of cocaine alone (5-20 mg/kg) resulted in no turning or minimal turning towards the lesioned side; the m...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1973.tb08156.x
更新日期:1973-01-01 00:00:00
abstract::The role of extracellular signal-regulated kinase (ERK)-1 and ERK-2 in controlling histamine-induced tone in bovine trachealis was investigated. PD 098059, an inhibitor of mitogen-activated protein kinase kinase (MKK)-1, had no effect on the histamine concentration-response relationship that described contraction. How...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703663
更新日期:2000-11-01 00:00:00
abstract::1. Dopamine is assumed to affect the ovary function after its conversion into noradrenaline (NA). 2. To study this bovine luteal slices from 11-14 days of the oestrous cycle were preincubated for 24 h to recover beta-receptors and next they were incubated for 1, 2 or 4 h with (a) different doses of dopamine; (b) dopam...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb15590.x
更新日期:1996-08-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Evidence suggests that phosphorylation of TRPV1 is an important component underlying its aberrant activation in pathological pain states. To date, the detailed pharmacology of diverse TRPV1 receptor agonists and antagonists has yet to be reported for native TRPV1 under phosphorylating conditions....
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.12005
更新日期:2013-02-01 00:00:00
abstract::1. The effects of beta-adrenoceptor blockade on the changes in plasma renin activity (PRA) following angiotensin enzyme (ACE) inhibition were investigated in pentobarbitone-chloralose anaesthetized dogs. 2. ACE-inhibition, with enalapril (2 mg kg-1), caused a significant reduction in systemic arterial blood pressure (...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1992.tb14338.x
更新日期:1992-06-01 00:00:00
abstract::1. The present study has compared the relative anti-aggregatory effect of various compounds which interfere with thromboxane (Tx) A2-dependent aggregation of human platelets in whole blood in vitro. These included the cyclo-oxygenase inhibitor aspirin, the TxA2 synthase inhibitor dazoxiben, the TxA2 (TP-) receptor blo...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1991.tb12200.x
更新日期:1991-02-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Pancreatic cancer is a solid tumour that is often fatal. Hence, there is an urgent need to identify new drug targets for this disease. Highly proliferating cancer cells have an increased demand for nutrients and, therefore, need to up-regulate selective amino acid transporters. Here, we investiga...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.13616
更新日期:2016-12-01 00:00:00
abstract::The effects of caffeine and procaine on noradrenergic transmission in the guinea-pig mesenteric artery were investigated by recording electrical responses of smooth muscle cells and by measuring the outflow of noradrenaline (NA) and 3,4-dihydroxyphenylglycol (DOPEG) induced by perivascular nerve stimulation. Caffeine ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1985.tb16149.x
更新日期:1985-03-01 00:00:00
abstract::1. The purpose of this study was to determine the in vivo inhibitory efficacy of azapropazone on neutrophil migration. The effects of azapropazone given at a dose of 100 mg kg-1 i.v. every 2 h on the neutrophil migration into skin inflammation sites (blister fluid) as well as into an autologous serum (+/- chemoattract...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1990.tb14686.x
更新日期:1990-02-01 00:00:00
abstract::1. We set out to elucidate the pharmacological mechanisms by which alpha 2-adrenoceptor and 5-HT-receptor ligands affect the haemodynamic response to acute central hypovolaemia in conscious rabbits. 2. Acute central hypovolaemia was produced by inflating an inferior vena caval cuff so that cardiac output fell at a con...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1993.tb13528.x
更新日期:1993-05-01 00:00:00
abstract::1. Incubation of bovine adrenal chromaffin cells with veratridine (10-100 microM) during 24 h, caused a concentration-dependent release of the cytosolic lactate dehydrogenase (LDH) into the bathing medium, an indicator of cell death. Lubeluzole or its R(-) enantiomer, R91154, did not enhance LDH release. Both lubeluzo...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701955
更新日期:1998-07-01 00:00:00
abstract::1. We have characterized the human smooth muscle endothelin converting enzyme (ECE) present in the media of the endothelium-denuded human umbilical vein preparation. 2. Endothelin-1 (ET-1) and ET-2 were potent constrictors of umbilical vein with EC50 values of 9.2 nM and 29.6 nM, respectively. ET-1 was at least 30 tim...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701564
更新日期:1997-12-01 00:00:00
abstract::1. Besides its antimuscarinic effects, propiverine may possess an additional mode of action. We compared the effects of propiverine, three of its metabolites (M-5, M-6, M-14) and atropine in human, pig and mouse urinary bladder preparations in order to elucidate the nature of a possible additional mode of action. 2. L...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0706244
更新日期:2005-07-01 00:00:00
abstract::Gene silencing techniques are gaining increasing popularity in the literature, both as a tool for unravelling gene function and to potentially deliver therapeutic benefit, especially in the context of cardiovascular disease. Gene-specific catalytic DNA molecules, or DNAzymes, have shown promise in ameliorating the eff...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1038/bjp.2008.145
更新日期:2008-06-01 00:00:00
abstract:BACKGROUND AND PURPOSE:AZ11645373 and N-{2-methyl-5-[(1R, 5S)-9-oxa-3,7-diazabicyclo[3.3.1]non-3-ylcarbonyl]phenyl}-2-tricyclo[3.3.1.13,7]dec-1-ylacetamide hydrochloride (compound-22) are recently described P2X(7) receptor antagonists. In this study we have further characterized these compounds to determine their mecha...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2009.00135.x
更新日期:2009-04-01 00:00:00
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 Noradrenaline and 28 imidazolidine (clonidine-like) and imidazoline (oxymetazoline-like) compounds with various phenyl ring substituents have been examined for their ability to inhibit responses to transmural stimulation and exogenous acetylcholine in ileal preparations from reserpine-treated guinea-pigs.2 The bathi...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1981.tb10429.x
更新日期:1981-06-01 00:00:00
abstract::1. The mechanism by which neuropeptide Y (NPY) potentiates the vasoconstriction induced by alpha 1-adrenoceptor agonists was investigated in 3rd generation mesenteric arterioles of the rat. 2. At a maximally active concentration, nitrendipine (10(-6) M) displaced to the right the concentration-response curves to norad...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1990.tb14714.x
更新日期:1990-02-01 00:00:00
abstract::1. Insulin antibodies were induced in young guinea-pigs of both sexes weighing 300-400 g and housed in a room maintained at 28 degrees C+/-2 degrees C, by subcutaneous injection of 2 ml of freshly prepared insulin antigen emulsion between the shoulders once every month.2. To estimate the titre of serum antibody the se...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1971.tb07087.x
更新日期:1971-05-01 00:00:00
abstract::1. Milacemide is a glycine prodrug which is both an inhibitor and a substrate for monoamine oxidase-type B (MAO-B) and also an inhibitor of MAO-type A (MAO-A). Its effects on dopamine and 5-hydroxytryptamine (5-HT) metabolism in rat frontal cortex tissue and dialysate were evaluated. 2. Dialysate dopamine concentratio...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1992.tb14210.x
更新日期:1992-01-01 00:00:00
abstract::1. Acetylcholine mustard (N-2-chloroethyl-N-methyl-2-acetoxyethylamine), a potent muscarinic agonist, binds virtually irreversibly to muscarinic receptors in longitudinal muscle strips from guinea-pig small intesting, as shown by the inhibition of the binding of E13-H]-propylbenzilycholine mustard ([3-H-PrBCM), an aff...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1975.tb07372.x
更新日期:1975-03-01 00:00:00
abstract::Anthracyclines can cause cumulative dose-related cardiotoxicity characterized by changes in Ca(2+) metabolism, including dysfunction of the sacroplasmic reticulum (SR) and decreased expression of Ca(2+)-handling proteins, such as the ryanodine receptor (RyR2). In this study, we examined the effect of dexrazoxane (ICRF...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703538
更新日期:2000-09-01 00:00:00