Abstract：
:1. We studied the ability of nitric oxide (NO) to physiologically antagonize endothelin-1 (ET-1) induced constrictions in human internal mammary artery (IMA). We also investigated the hypothesis that NO interacts directly with ET-receptor binding in human heart and aorta. 2. ET-1 potently contracted IMA (EC(50) 6.86 nM, 95% CI: 3.5 - 13.4 nM; n=12). The constrictor response to 10 nM ET-1 was fully reversed by the NO-donor diethylamine NONOate (DEA/NO; EC(50) 2.0 microM, 95% CI: 0.8 - 4.8 microM; n=5). The guanylate cyclase inhibitor ODQ (100 microM) reduced the response to DEA/NO but did not abolish it (E(MAX) 50.9+/-8.5% in the presence of ODQ; 113.0+/-8.4%, control). 3. The increase in cyclic GMP by 30 microM DEA/NO was abolished in the presence of 100 microM ODQ (n=6). 4. In saturation binding experiments the NO-donor Diethyltriamine NONOate (DETA/NO; 1 mM) caused a 90% reduction in maximum binding of [(125)I]-ET-1 in human heart, without affecting the affinity. This reduction in binding was abolished by haemoglobin. Pre-incubating either the radiolabel or the tissue with NO-donors did not reduce binding. A similar effect was observed in aortic smooth muscle. 5. We have shown that DEA/NO is able to reverse ET-1-induced contractions in the human vasculature. The binding studies suggest a direct interaction between NO and the ET receptor or receptor-ligand complex in human ventricular and aortic tissue. NO is released continuously in vivo, thus this apparent modification of ET-receptor binding may provide an additional mechanism by which NO counter-balances the effects of ET.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Wiley KE,Davenport APdoi
10.1038/sj.bjp.0703834subject
Has Abstractpub_date
2001-01-01 00:00:00pages
213-20issue
1eissn
0007-1188issn
1476-5381journal_volume
132pub_type
杂志文章abstract：:The diterpene, forskolin, is shown to produce a concentration-dependent, increase in short circuit current in two epithelial preparations, amphibian skin and rat colon. In the amphibian tissue the increase is sensitive to amiloride and due to an increase in electrogenic transepithelial sodium transport towards the ser...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1982.tb09187.x
更新日期：1982-05-01 00:00:00
abstract：:1. Human epicardial coronary artery rings, freshly obtained from cardiac transplant patients, were examined for their responses to endothelium-derived relaxing factor (EDRF)-releasing agents. 2. Functional antagonism profoundly influenced relaxation responses in this tissue. Increasing force with concentrations of U46...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1994.tb17109.x
更新日期：1994-12-01 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：:1. The modulation of L-type calcium channel current (ICa) by fendiline, a diphenylalkylamine type of calcium channel blocker was investigated on guinea-pig ventricular myocytes by use of the whole-cell patch-clamp technique. 2. Fendiline-induced block of ICa is accompanied by modulation of the channel kinetics in a co...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1992.tb14308.x
更新日期：1992-05-01 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...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1989.tb12001.x
更新日期：1989-07-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Hepatic encephalopathy is a neuropsychiatric disorder of complex pathogenesis caused by acute or chronic liver failure. We investigated the effects of cannabidiol, a non-psychoactive constituent of Cannabis sativa with anti-inflammatory properties that activates the 5-hydroxytryptamine receptor 5...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2010.01179.x
更新日期：2011-04-01 00:00:00
abstract：:Liver X receptors (LXRs) are members of the nuclear receptor superfamily that are canonically activated by oxidized derivatives of cholesterol. Since the mid-90s, numerous groups have identified LXRs as endocrine receptors that are involved in the regulation of various physiological functions. As a result, when their ...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.15286
更新日期：2020-10-20 00:00:00
abstract：:1. Thoracic aortae, isolated from rats supplemented with dietary vitamin E after vitamin E deficiency, were analysed for changes in vascular reactivity. 2. Following 4 or 12 months of dietary vitamin E deficiency, endothelium-dependent vasodilator responses to acetylcholine were significantly impaired. However, when a...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1994.tb13103.x
更新日期：1994-06-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Toll-like receptor 4 (TLR4) signalling contributes to inflammatory cardiovascular diseases, but its role in hypertension and the associated vascular damage is not known. We investigated whether TLR4 activation contributed to angiotensin II (AngII)-induced hypertension and the associated vascular ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.13117
更新日期：2015-06-01 00:00:00
abstract：:1. Nicotine can activate primary afferent nociceptors, one result of which is to increase neurogenic plasma extravasation. In this study we have demonstrated a novel proinflammatory effect of sub-nanomolar nicotine, mediated by peripheral action at sensory neurons. This action is normally masked by adrenal medulla-der...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0704031
更新日期：2001-05-01 00:00:00
abstract：:1. The aim of the present study was to examine whether ramipril induces delayed myocardial protection against free radical injuries ex vivo and to determine the possible role of the bradykinin B2-nitric oxide (NO) pathway, prostaglandins(PGs) and protein synthesis in this delayed adaptive response. 2. Rats were pretre...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702089
更新日期：1998-10-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Much interest is currently being focused on the anti-nociceptive effects mediated by nicotinic acetylcholine (nACh) receptors, including their location and mechanism of action. The purpose of this study was to elucidate these issues using 5-iodo-3-(2(S)-azetidinylmethoxy)pyridine (5IA), a nACh re...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2009.00613.x
更新日期：2010-03-01 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:The non-nucleoside analogue reverse transcriptase inhibitor efavirenz is associated with hepatic toxicity and metabolic disturbances. Although the mechanisms involved are not clear, recent evidence has pinpointed a specific mitochondrial action of efavirenz accompanied by the induction of an endo...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.13018
更新日期：2015-04-01 00:00:00
abstract：:1 The binding of [3H]-muscimol, a potent gamma-aminobutyric acid (GABA) receptor agonist, to crude membrane preparations of bovine retina was studied, using a filtration method to isolate membrane-bound ligand. 2 Specific binding was found to be saturable and occurred at two binding sites with affinity constants of 4....
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1980.tb10934.x
更新日期：1980-01-01 00:00:00
abstract：:1. The modulation of the gamma-aminobutyric acidA (GABAA) receptor by reduced metabolites of progesterone and deoxycorticosterone has been compared with that produced by depressant barbiturates in: (a) voltage-clamp recordings from bovine enzymatically isolated chromaffin cells in cell culture, and (b) an assay of the...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1988.tb11646.x
更新日期：1988-08-01 00:00:00
abstract：:1. The current study investigated the effects of respiratory tract viral infection on the density of ETA and ETB receptors in murine tracheal smooth muscle and on the contractile response to endothelin-1 mediated by these receptors. 2. Quantitative autoradiographic studies using [125I]-endothelin-1 revealed that trach...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1994.tb13209.x
更新日期：1994-08-01 00:00:00
abstract：:1. This study exploited established immunoneutralization protocols and an N-terminal annexin 1 peptide (annexin 1(Ac2 - 26)) to advance our knowledge of the role of annexin 1 as a mediator of acute glucocorticoid action in the rat neuroendocrine system in vivo. 2. Rats were treated with corticosterone (500 microg kg(-...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0704324
更新日期：2001-10-01 00:00:00
abstract：BACKGROUND AND PURPOSE:The beneficial effect of 5-HT6 receptor antagonism in cognition remains controversial. This study has been undertaken to reassess the cognition enhancing properties of acute vs subchronic treatment with the selective 5-HT6 receptor antagonist SB-271046 in unimpaired rats, as well as against scopo...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/bjp.2008.281
更新日期：2008-10-01 00:00:00
abstract：:1. Neurogenic responses to transmural electrical stimulation were examined in endothelium-denuded extrameningeal (vertebral and carotid) and intrameningeal (spinal, basilar and middle cerebral) arteries isolated from dogs. 2. In the extrameningeal arteries, transmural electrical stimulation produced a phasic contracti...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1995.tb17207.x
更新日期：1995-11-01 00:00:00
abstract：:The mechanism underlying the LTC(4)-induced contraction of guinea-pig taenia coli was determined using the simultaneous measurements of [Ca(2+)](i) and force in whole muscle preparations. Additional experiments were performed in receptor coupled permeabilized preparation. For comparison purposes, the contraction which...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0704122
更新日期：2001-06-01 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：:The effect of fluoxetine on uptake of 5-hydroxytryptamine (5-HT) by enteric 5-hydroxytryptaminergic neurones has been analyzed in order to compare further these neurones with 5-HT neurones of the CNS. In addition, the effects of fluoxetine and chlorimipramine on efflux of [3H]-5-HT from the myenteric plexus were also ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1979.tb16089.x
更新日期：1979-05-01 00:00:00
abstract：:1. Histamine (2-4 micrograms kg-1 i.v.) increased airways resistance (Raw) and decreased dynamic lung compliance (Cdyn) in urethane-anaesthetized guinea-pigs. The effects on Raw were almost abolished by atropine (0.1 mg kg-1 i.v.) and reduced by vagal cooling (11-16 degrees C). 2. Histamine-induced changes in Raw and ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1988.tb11555.x
更新日期：1988-06-01 00:00:00
abstract：:1. Experiments were designed to determine whether endothelium-dependent relaxing factor(s) released by acetylcholine from the canine femoral artery influences the membrane potential of coronary arterial smooth muscle. 2. The membrane potential was recorded in small canine coronary arteries (internal diameter less than...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1988.tb10306.x
更新日期：1988-03-01 00:00:00
abstract：:1. Isolated preparations of rat anococcygeus muscle were incubated with [3H]-noradrenaline and the efflux of radioactivity induced by stimulation of intramural sympathetic nerves was used as a measure of release of transmitter noradrenaline. Isometric contractile responses were also measured. 2. Angiotensin I (0.03 mi...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1988.tb11657.x
更新日期：1988-10-01 00:00:00
abstract：:1. Protein phosphorylation is involved in the induction of nitric oxide synthase II (NOS II, iNOS) in several types of animal cells. Here we have investigated the possible involvement of major protein kinases in the induction of NOS II expression in human DLD-1 cells. 2. In DLD-1 cells, interferon--gamma alone induced...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701782
更新日期：1998-04-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Diabetes mellitus is associated with a specific cardiomyopathy. We compared the cardioprotective effects of an endothelin-A receptor blocker (ET(A)-RB) with those of an angiotensin-converting enzyme inhibitor (ACE-I) in rats with streptozotocin (STZ)-induced diabetes. EXPERIMENTAL APPROACH:Diabe...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0707325
更新日期：2007-08-01 00:00:00
abstract：:The Concise Guide to PHARMACOLOGY 2015/16 provides concise overviews of the key properties of over 1750 human drug targets with their pharmacology, plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand propert...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.13350
更新日期：2015-12-01 00:00:00
abstract：:1. Unique among the phospholipids, phosphatidylserine depresses brain energy metabolism when injected intravenously into mice in the form of sonicated liposomes. The possibility that this effect results from a metabolic transformation of phosphatidylserine is examined in this paper. 2. A strong enhancement of the phos...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1979.tb08708.x
更新日期：1979-12-01 00:00:00
