Abstract:
:The stoichiometric relationship between adrenoceptors and saturable binding sites for 1,4-dihydropyridines in calcium channels was investigated in human ventricular myocardium. Membrane particles were prepared from heart specimens of patients undergoing open heart surgery. The patients suffered from hypertrophic obstructive cardiomyopathy (HOCM) or mitral valve disease. Using [3H]-prazosin and [125I]-2-beta-hydroxy-3-iodiphenyl-ethyl-aminoethyl tetralone ([125I]-HEAT) as labels we detected only a marginal density of alpha 1-adrenoceptors, regardless of disease. No alpha 2-adrenoceptors were detected with [3H]-rauwolscine. In HOCM patients we estimated 72 +/- 10 fmol mg-1 (n = 12) beta-adrenoceptors labelled with [3H]-(-)-dihydroalprenolol and 74 +/- 5 fmol mg-1 (n = 2) beta-adrenoceptors labelled with [125I]-(-)-iodocyanopindolol; the equilibrium dissociation constants KD, were 1.2 +/- 0.2 nmol l-1 for [3H]-(-)-dihydroalprenolol and 7 +/- 1 pmol l-1 for [125I]-(-)-iodocyanopindolol. In patients with mitral valve disease we estimated 84 +/- 11 fmol mg-1 (n = 3) labelled with [3H]-(-)-dihydroalprenolol and 66 +/- 13 fmol mg-1 (n = 2) labelled with [125I]-(-)-iodocyanopindolol. The KD values were 1.8 +/- 0.6 nmol l-1 for [3H]-(-)-dihydroalprenolol and 8 +/- 2 pmol l-1 for [125I]-(-)-iodocyanopindolol. In 14 HOCM patients we estimated 107 +/- 12 fmol mg-1 calcium channel sites labelled with [3H]-nimodipine with a KD of 280 +/- 4 pmol l-1. In 5 patients with mitral valve disease the density of calcium channel sites labelled with [3H]-nimodipine was 78 +/- 5 fmol mg-1 with a KD of 290 +/- 20 pmol l-1, In HOCM patients the density of calcium channel sites labelled with the benzoxadiazol 1,4-dihydropyridine ([3H]-(+)-PN 200-110) was 1.6 fold of that labelled with [3H]-nimodipine with a KD of 84 +/- 11 pmol l-1. In a group of 4 HOCM patients in which calcium channels were labelled with [125I]-iodipine, the density of sites was 1.37 +/- 0.07 fold the density of sites labelled by [3H]-(+)-PN 200-11-. The KD value of [125I]-iodipine was 246 +/- 16 pmol-1. (+)-PN 200-110 was approximately 100 fold more potent than (-)-PN 200-110 as a competitor of [125I]-iodipine binding. For the HOCM group a significant correlation was found between beta-adrenoceptor density and calcium channel density, whereas in the mitral valve group no such correlation was found. This does not prove that there is causal interaction leading to a relationship between the density of beta-adrenoceptors and calcium channels. However, because positive inotropic effects of catecholamines mediated by beta-adrenoceptors are associated with opening of calcium channels, this suggests that the density of both beta-adrenoceptors and calcium channels could be co-regulated.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Ferry DR,Kaumann AJdoi
10.1111/j.1476-5381.1987.tb11194.xsubject
Has Abstractpub_date
1987-03-01 00:00:00pages
447-57issue
3eissn
0007-1188issn
1476-5381journal_volume
90pub_type
杂志文章abstract::1. The effect of 1-aminocyclopropanecarboxylic acid (ACPC), a partial agonist at the glycine site of the N-methyl-D-aspartate (NMDA) receptor complex that exhibits neuroprotective, anxiolytic and antidepressant-like actions, was investigated in a functional assay for presynaptic NMDA receptors. 2. NMDA (100 microM) pr...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb15484.x
更新日期:1996-06-01 00:00:00
abstract::1. Chronic benzodiazepine administration has been associated with tolerance and with downregulation of gamma-aminobutyric acidA (GABAA)-receptor binding and function. However, effects of individual benzodiazepines on brain regions have varied. 2. To compare the effects of chronic lorazepam and alprazolam, we have admi...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1990.tb14167.x
更新日期:1990-12-01 00:00:00
abstract::1. The action of adrenaline on the K(+) balance of the isolated heart was found to depend on the ionic composition and the temperature of the perfusion fluids used.2. When the perfusion fluid contained 145 mM Na(+), 1.7 mM Ca(++) and 3-9 mM K(+), adrenaline caused the hearts to gain K(+); when the K(+) concentration w...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1969.tb08012.x
更新日期:1969-07-01 00:00:00
abstract::The phenanthrene-derivative 9-phenanthrol is a recently identified inhibitor of the transient receptor potential melastatin (TRPM) 4 channel, a Ca(2+) -activated non-selective cation channel whose mechanism of action remains to be determined. Subsequent studies performed on other ion channels confirm the specificity o...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bph.12582
更新日期:2014-04-01 00:00:00
abstract::1. ZENECA ZD7288 (4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino) pyrimidinium chloride, formerly ICI D7288) is a novel sino-atrial node function modulator which selectively slows sinus node rate. Its effects on haemodynamic function have been studied in pentobarbitone anaesthetized dogs, in comparison with zat...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1994.tb17101.x
更新日期:1994-11-01 00:00:00
abstract::1. Our study was aimed at investigating the duration of the bronchodilator action of the antimuscarinc drug glycopyrrolate compared to tiotropium and ipratropium. In the guinea-pig isolated trachea, the time (t1/2) necessary for a contractile response to carbachol (0.3 microM) to return to 50% recovery after washout o...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0706724
更新日期:2006-06-01 00:00:00
abstract::1. The kinetics of glycine-sensitive, N-methyl-D-aspartate (NMDA) receptor desensitization were investigated in cultured neurones with the patch clamp technique. 2. The degree of fast NMDA-receptor desensitization was inversely related to glycine concentration. Thus, increasing concentrations of glycine from 30 nM to ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1993.tb13556.x
更新日期:1993-05-01 00:00:00
abstract::The Wnt/β-catenin signalling pathway is pivotal for stem cell function and the control of cellular differentiation, both during embryonic development and tissue homeostasis in adults. Its activity is carefully controlled through the concerted interactions of concentration-limited pathway components and a wide range of...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bph.14038
更新日期:2017-12-01 00:00:00
abstract::The neonate has an unusual capacity for survival and the possibility exists that mechanisms for controlling stress responses may differ in the developing animal. In adults both endogenous and exogenous opioids can modulate the corticosterone responses to stress. We have studied this effect in neonatal rats and found t...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1987.tb08990.x
更新日期:1987-05-01 00:00:00
abstract::Forty-eight isolated rat hearts were perfused with Krebs solution and with [(3)H]-(-)-noradrenaline ([(3)H]-NA) containing 4.5 nCi/ml in 50 ng/ml, as described by Iversen (1963). To groups of six, cocaine was added to [(3)H]-NA in concentrations of 400 nM, 2 and 10 muM. To the rest Tween 80, 25 mug/ml was added to [(3...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1974.tb10686.x
更新日期:1974-07-01 00:00:00
abstract::1. The pathological features of Gram-positive shock can be mimicked by the co-administration of two cell wall components of Staphylococcus aureus, namely lipoteichoic acid (LTA) and peptidoglycan (PepG). This is associated with the expression of the inducible isoform of nitric oxide synthase (iNOS) in various organs. ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb16053.x
更新日期:1996-12-01 00:00:00
abstract::1. Inhibition of mechanical activity in longitudinal muscle strips of rabbit duodenum was induced by perivascular and intramural nerve stimulation.2. The effects of perivascular stimulation were abolished by phentolamine + propranolol, guanethidine, reserpine and by tetrodotoxin. The effects of intramural stimulation ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1973.tb06916.x
更新日期:1973-06-01 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:BACKGROUND AND PURPOSE:Pancreatic cancer is characterized by alterations in several key signalling proteins, including increased expression and activity of the Src tyrosine kinase and focal adhesion kinase (FAK), which have been linked to its chemoresistance. Sustained Src inhibition reactivates survival pathways regul...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.12855
更新日期:2015-01-01 00:00:00
abstract::1 The metabolism of extracellular nucleotides plays an important role in nucleotide signalling mediated by P2 receptors. The nucleotide sequence encoding a putative human ecto-ATPase named CD39L1 was reported recently. However, the biological activity of this protein has not been established. 2 Based on the sequence o...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702805
更新日期:1999-09-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Selective and potent antagonists for the β(2) -adrenoceptor are potentially interesting as experimental and clinical tools, and we sought to identify novel ligands with this pharmacology. EXPERIMENTAL APPROACH:A range of pharmacological assays was used to assess potency, affinity, selectivity (β...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2011.01269.x
更新日期:2011-09-01 00:00:00
abstract::1. The effects of the muscarinic agonist carbachol on phosphoinositide metabolism and its relationship to alteration of intracellular calcium were examined in SK-N-SH human neuroblastoma cells. Muscarinic receptors on these cells are coupled to phospholipase C and the myo [2-3H]-inositol phosphates resulting from rece...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1989.tb12681.x
更新日期:1989-12-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Glucocorticoids appear to control Na⁺ absorption in pulmonary epithelial cells via a mechanism dependent upon serum and glucocorticoid-inducible kinase 1 (SGK1), a kinase that allows control over the surface abundance of epithelial Na⁺ channel subunits (α-, β- and γ-ENaC). However, not all data s...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2012.01860.x
更新日期:2012-06-01 00:00:00
abstract::1 The effects of isoprenaline, propranolol and phosphodiesterase inhibitors on (3)H-transmitter overflow elicited by low frequency nerve stimulation were determined in the isolated perfused spleen of the cat.2 (-)-Isoprenaline (0.14, 1.4, and 14 nM) produced a concentration-dependent increase in [(3)H]-transmitter ove...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1978.tb07779.x
更新日期:1978-05-01 00:00:00
abstract::1. A comparative study was carried out to assess the regional haemodynamic effects of intravenous infusion of human alpha- and beta-calcitonin gene-related peptide (CGRP; 0.006, 0.06 and 0.6 nmol h-1) in conscious, unrestrained Wistar rats. 2. With human alpha-CGRP, tachycardia was always accompanied by a fall in mean...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1989.tb12668.x
更新日期:1989-12-01 00:00:00
abstract::1. The effects of 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), an inhibitor of soluble guanylyl cyclase (sGC), were investigated in aortic rings and ventricular cardiomyocytes from rats. The production of cyclic GMP was stimulated by NO.-donors or carbachol. Additionally, the effects of ODQ were studied in cytos...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702608
更新日期:1999-06-01 00:00:00
abstract::1. The influence of feeding 2 levels of sotalol on the incidence of beta-aminopropionitrile (BAPN)-induced aortic ruptures of immature turkeys was determined.2. Four of 22 turkeys fed 0.12% sotalol and 0.07% BAPN died of aortic ruptures, but 6 of 21 turkeys fed only BAPN died of the syndrome.3. Blood pressure, heart r...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1972.tb08095.x
更新日期:1972-07-01 00:00:00
abstract::1 The relative potencies of methotrimeprazine, (+)-methotrimeprazine, (+/-)-10-(3-dimethylamino-2-methylpropyl)-2-valeroyl phenothiazine hydrochloride (M & B 18,706) and (+)-M & B 18,706 in reducing the pressor action of noradrenaline in the spinal cat, reducing intercollicular decerebrate rigidity, and muscle spindle...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1974.tb09610.x
更新日期:1974-03-01 00:00:00
abstract::1. Inhibition of rat platelet aggregation by the nitric oxide (NO) donor MAHMA NONOate (Z-1-N-methyl-N-[6-(N-methylammoniohexyl)amino]diazen-1-ium-1,2-diolate) was investigated. The aims were to compare its anti-aggregatory effect with vasorelaxation, to determine the effects of the soluble guanylate cyclase inhibitor...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704971
更新日期:2002-12-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Lithocholic acid (LCA), the most toxic bile acid, induces cholestatic liver injury in rodents. We previously showed that LCA activates the oxidative stress-responsive nuclear factor (erythroid-2 like), factor 2 (Nrf2) in cultured liver cells, triggering adaptive responses that reduce cell injury....
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2010.00953.x
更新日期:2010-11-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Dysfunction and injury of endothelial cells in the pulmonary artery play critical roles in the hypertension induced by chronic hypoxia. One consequence of hypoxia is increased activity of 15-hydroxyprostaglandin dehydrogenase (PGDH). Here, we have explored, in detail, the effects of hypoxia on th...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.12594
更新日期:2014-07-01 00:00:00
abstract::Two splice isoforms of rabbit alpha(1a)-adrenergic receptor (AR), (named alpha(1a)-OCU.2-AR and alpha(1a)-OCU.3-AR) have been isolated from the liver cDNA library in addition to the previously reported isoform (alpha(1a)-OCU.1-AR). Although they have the identical splice position with human alpha(1a)-AR isoforms, the ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703242
更新日期:2000-04-01 00:00:00
abstract::1. Recent studies have shown that sodium butyrate and other short-chain fatty acids (SCFAs) can prevent inflammation in colon diseases. Our aim was to elucidate whether sodium butyrate and SCFAs regulate the inflammatory responses in different neural inflammation models in cell cultures. 2. Inflammatory responses to L...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705682
更新日期:2004-03-01 00:00:00
abstract::1. The efflux and influx of tryptophan across the synaptosomal plasma membrane has been studied under a variety of experimental conditions, in order to examine the mechanism by which depolarization enhances the efflux of tryptophan from superfused synaptosomes. 2. Efflux of [3H]-tryptophan from preloaded superfused sy...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1988.tb11440.x
更新日期:1988-02-01 00:00:00
abstract:BACKGROUND AND PURPOSE:The human prostacyclin receptor (hIP), a G-protein coupled receptor (GPCR) expressed mainly on platelets and vascular smooth muscle cells, plays important protective roles in the cardiovascular system. We hypothesized that significant insights could be gained into the structure and function of th...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0707413
更新日期:2007-10-01 00:00:00