Abstract:
:1. Release-regulating alpha 2-autoreceptors in human brain were characterized pharmacologically in cortical slices from patients undergoing neurosurgery to remove subcortical tumours; the slices were prelabelled with [3H]-noradrenaline ([3H]-NA) and stimulated electrically (3 Hz, 2 ms, 24 mA) under superfusion conditions. 2. The stimulus-evoked tritium overflow was almost totally Ca(2+)-dependent and tetrodotoxin-sensitive. 3. Clonidine and oxymetazoline 0.01 to 1 microM inhibited in a concentration-dependent manner the evoked overflow of tritium. The two drugs were equipotent (EC50 = 0.03 microM) and their maximal effect was approx. 45%. Phenylephrine and methoxamine, up to 1 microM, did not affect tritium overflow. 4. Yohimbine (0.01-0.1 microM) shifted the concentration-response curve of clonidine to the right. The calculated pA2 value was 8.29. 5. Prazosin and 2-[2-[4-(o-methoxyphenyl)piperazine-1-yl]ethyl]-4,4- dimethyl-1,3(2H,4H)-isoquinolinedione (AR-C 239), tested at 0.3 microM, did not modify the concentration-response curve of clonidine. 6. The effect of clonidine was antagonized by (+)-mianserin (pA2 = 7.74), but not by up to 0.3 microM of the (-)-enantiomer. The concentration-response curve of clonidine was shifted to the right by the novel alpha 2-adrenoceptor antagonist, 5-chloro-4-(1-butyl-1,2,5,6-tetrahydropyridin-3-yl)-thiazole-2-ami ne (Z)-2-butenedioate (1:1) salt (ORG 20350) (pA2 = 7.55). 7. Yohimbine, (+)-mianserin and ORG 20350, but not prazosin and (-)-mianserin, increased the electrically-evoked tritium overflow, suggesting that autoreceptors may be tonically activated by endogenous NA. 8. Desipramine (1 microM) increased evoked tritium overflow from human cortex slices. The effect of clonidine (0.01- 1 g1M) on the evoked overflow of tritium was reduced in presence of 1 muM desipramine.9. It is proposed that autoregulation of NA release can occur in human cerebral cortex. The process involves activation of alpha 2-adrenoceptors which may be either the alpha2X or the alpha2D subtype.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Raiteri M,Bonanno G,Maura G,Pende M,Andrioli GC,Ruelle Adoi
10.1111/j.1476-5381.1992.tb13421.xsubject
Has Abstractpub_date
1992-12-01 00:00:00pages
1146-51issue
4eissn
0007-1188issn
1476-5381journal_volume
107pub_type
杂志文章abstract::1. The effects of acetylcholine (ACh) on membrane potential, relaxation and cyclic GMP levels were compared to the NO donor L-nitrosocysteine (Cys-NO) in segments of guinea-pig coronary artery. 2. ACh and Cys-NO produced concentration-dependent relaxations of muscles contracted with the H1 receptor agonist, 2-(2-amino...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1994.tb14851.x
更新日期:1994-04-01 00:00:00
abstract::1 A procedure involving two guinea-pig isolated hearts perfused in series is described for detecting in the recipient heart the release of a possible coronary vasodilator metabolite from the donor heart. 2 Adrenaline and isoprenaline stimulated the rate and force of contraction and produced a multiphasic coronary vasc...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1976.tb07696.x
更新日期:1976-09-01 00:00:00
abstract::The effect of baclofen, the GABAB-agent, on the potassium-evoked release of endogenous 5-hydroxytryptamine (5-HT) from slices of mouse frontal cortex has been investigated. The release of endogenous 5-HT evoked by addition of K+ (35 mM) was inhibited by (+/-)-baclofen in a dose-dependent manner with an IC50 of 0.1 mic...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1987.tb11244.x
更新日期:1987-07-01 00:00:00
abstract::1. The affinities of a number of alpha 1-adrenoceptor antagonists were determined by displacement of [3H]-prazosin binding from cloned human alpha 1A-adrenoceptors (previously designated cloned alpha 1c subtype), alpha 1B alpha 1D and rat alpha 1D-adrenoceptors, stably expressed in rat-1 fibroblasts. Functional affini...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb15907.x
更新日期:1995-07-01 00:00:00
abstract::1. The role of adenosine 3':5'-cyclic monophosphate (cyclic AMP) in the regulation of catecholamine (CA) secretion in chromaffin cells remains equivocal from previous studies. 2. In the present study the effect of this cyclic nucleotide on basal CA secretion, as well as on intracellular calcium and membrane potential ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb13257.x
更新日期:1995-01-01 00:00:00
abstract::This work investigates the receptor acted upon by imidazoline compounds in the modulation of morphine analgesia. The effects of highly selective imidazoline ligands on the supraspinal antinociception induced by morphine in mice were determined. 2. Intracerebroventricular (i.c.v.) or subcutaneous (s.c.) administration ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703294
更新日期:2000-05-01 00:00:00
abstract::AMPA-type glutamate receptors are one of the most dynamic components of excitatory synapses. Their regulated addition and removal from synapses leads to long-lasting forms of synaptic plasticity, known as long-term potentiation (LTP) and long-term depression (LTD). In addition, AMPA receptors reach their synaptic targ...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1038/sj.bjp.0707525
更新日期:2008-03-01 00:00:00
abstract:LINKED ARTICLES:This article is part of a themed section on Nitric Oxide 20 Years from the 1998 Nobel Prize. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.2/issuetoc. ...
journal_title:British journal of pharmacology
pub_type: 社论
doi:10.1111/bph.14540
更新日期:2019-01-01 00:00:00
abstract::1. Intrathecal (i.t.) administration of nociceptin and high doses of morphine induced allodynia in response to innocuous tactile stimuli, and i.t. nociceptin evoked hyperalgesia in response to noxious thermal stimuli in conscious mice. Here we have characterized the nociceptin-induced allodynia and compared it with th...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701146
更新日期:1997-06-01 00:00:00
abstract::1. The effects of cromakalim (BRL 34915) on the smooth muscle cells of guinea-pig mesenteric artery and vein were investigated with microelectrode and tension recording methods. 2. Cromakalim (greater than 10 microM) produced membrane hyperpolarization with an increase in ionic conductance. The hyperpolarization occur...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1988.tb11707.x
更新日期:1988-11-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Thromboxane A(2) and endothelial dysfunction are implicated in the development of pulmonary hypertension. The receptor-transduction pathway for U46619 (9,11-dideoxy-9 alpha, 11 alpha-methanoepoxy prostaglandin F(2 alpha))-induced contraction was examined in endothelium-intact (E+) and denuded (E-...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2008.00084.x
更新日期:2009-06-01 00:00:00
abstract::1. Pharmacological inhibitors of protein kinase A (PKA) and protein phosphatases 1/2A were used to determine whether basal L-type Ca(2+) current (I(Ca)) observed in the absence of exogenous beta-adrenergic receptor stimulation is sustained by PKA-mediated phosphorylation. Amphotericin B was used to record whole-cell I...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0706809
更新日期:2006-08-01 00:00:00
abstract::1. We have investigated the in vitro interaction between chloride ions and endothelium as revealed by alterations in vascular contractility and smooth muscle cell membrane potential in isolated pulmonary arteries from Dahl salt-resistant normotensive and salt-sensitive hypertensive rats. 2. Exposure to nitro-l-arginin...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705703
更新日期:2004-03-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Endogenous cannabinoids (endocannabinoids) in the periaqueductal grey (PAG) play a vital role in mediating stress-induced analgesia. This analgesic effect of endocannabinoids is enhanced by pharmacological inhibition of their degradative enzymes. However, the specific effects of endocannabinoids ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.12839
更新日期:2014-12-01 00:00:00
abstract:BACKGROUND AND PURPOSE:N-arachidonyl dopamine (NADA) has been identified as a putative endocannabinoid, but there is little information about which signalling pathways it activates. The purpose of this study was to identify the signalling pathways activated by NADA in vitro. EXPERIMENTAL APPROACH:Human or rat cannabin...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.13341
更新日期:2016-01-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Preclinical cardiovascular safety studies (CVS) have been compared between facilities with respect to their sensitivity to detect drug-induced QTc prolongation (ΔQTc). Little is known about the consistency of quantitative ΔQTc predictions that are relevant for translation to humans. EXPERIMENTAL...
journal_title:British journal of pharmacology
pub_type: 杂志文章,meta分析
doi:10.1111/bph.13218
更新日期:2015-09-01 00:00:00
abstract::1. The effects of dopamine on the L-type Ca2+ current (ICa,L) of both atrial and ventricular single myocytes and on the force of contraction of atrial trabeculae in rat heart were investigated. 2. Dopamine increased atrial ICa,L at concentrations higher than 1 microM, but had little or no effect on ICa,L at lower conc...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701250
更新日期:1997-08-01 00:00:00
abstract::1. Endotoxin shock is accompanied by an increase in peripheral vascular permeability. It has been postulated that most biological activities of LPS are derived from lipid A moiety. Here we examined the effect of lipid A analogue ONO-4007 in increasing vascular permeability and the possible mediators in mouse skin by a...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703425
更新日期:2000-07-01 00:00:00
abstract::1. Vanadium compounds can mimic actions of insulin through alternative signalling pathways. The effects of three organic vanadium compounds were studied in non-ketotic, streptozotocin-diabetic rats: vanadyl acetylacetonate (VAc), vanadyl 3-ethylacetylacetonate (VEt), and bis(maltolato)oxovanadium (VM). A simple inorga...
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pub_type: 杂志文章
doi:10.1038/sj.bjp.0702311
更新日期:1999-01-01 00:00:00
abstract::Ischaemia is amongst the leading causes of death. Despite this importance, there are only a few therapeutic approaches to protect from ischaemia-reperfusion injury (IRI). In experimental studies, the amino acid glycine effectively protected from IRI. In the prevention of IRI by glycine in cells and isolated perfused o...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
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更新日期:2012-04-01 00:00:00
abstract::1. The effects of myocardial ischaemia/reperfusion were tested on the coronary vasorelaxant responses to agonists selective for the A1 and A2 adenosine receptor subtypes in the dog. The left anterior descending (LAD) coronary artery was occluded distal to the first diagonal branch. The occlusion was maintained for 1 h...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1994.tb14877.x
更新日期:1994-04-01 00:00:00
abstract::1. Phenylephrine-induced contractions of rabbit isolated trigone and urethra were antagonized in a competitive manner by alfuzosin (pA2 7.44 and 7.30, respectively) and prazosin. 2. The characteristics of [3H]-prazosin binding to human prostatic adenoma tissue were evaluated. [3H]-prazosin was potently displaced by al...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1993.tb13762.x
更新日期:1993-08-01 00:00:00
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::1 Thermic oedema induced by heating rat paws at 46.5 degrees C was potentiated by local injection of adrenaline, noradrenaline or high doses of isoprenaline. The pro-inflammatory effect of sympathomimetic amines was antagonized by phenoxybenzamine or phentolamine but not by propranolol.2 The subcutaneous space of heat...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1974.tb08568.x
更新日期:1974-02-01 00:00:00
abstract::1. Ischaemic preconditioning (IP) protects the myocardium against irreversible ischaemic injury by activating protein kinase C (PKC). The mechanism by which PKC protects the myocardium is unknown. We have shown that PKC increases the activity of ecto-5'-nucleotidase (ecto-5'-N) and thereby the production of adenosine ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0700890
更新日期:1997-01-01 00:00:00
abstract::1. The effect of prostaglandin E1 (PGE1) on the spontaneous phasic contraction of the rat isolated portal vein was studied. 2. The isolated portal vein exhibited spontaneous phasic contractions. Removal of Ca2+ from Krebs-Ringer solution or application of nifedipine abolished the spontaneous contraction, indicating th...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701051
更新日期:1997-04-01 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. Recent studies demonstrated that the cardiac calpain system is activated during ischaemic events and is involved in cardiomyocyte injury. The aim of this study was to investigate the contribution of AT(1) and AT(2) receptors in the regulation of calpain-mediated myocardial damage following myocardial infarction (MI...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703860
更新日期:2001-02-01 00:00:00
abstract::1. The effects of 5-hydroxytryptamine (5-HT) uptake inhibitors, agonists and antagonists have been evaluated on mouse marble-burying behaviour, a putative test for anxiolytic agents. The high levels of locomotor activity occurring on first exposure to a circular runway (runway were used as a separate test of non-speci...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1991.tb12392.x
更新日期:1991-09-01 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