Abstract:
:1 Rabbit isolated hearts, perfused by the Langendorff technique, were used to investigate the indirect sympathomimetic effects of 5-hydroxytryptamine (5-HT). Comparisons were made with noradrenaline and with two indirectly acting sympathomimetic agents with entirely different mechanisms of action, tyramine and dimethylphenylpiperazinium (DMPP). 2 The cardiac stimulant effects of 5-HT, tyramine and DMPP were inhibited by propranolol and practolol and the pA2 values obtained were similar to those obtained with noradrenaline as the agonist. 3 Responses to 5-HT, tyramine and DMPP were greatly reduced on hearts from rabbits pretreated with 6-hydroxydopamine. Such hearts had less than 7% of their normal catecholamine concentration and no fluorescence characteristic of noradrenaline in the cardiac sympathetic nerves could be demonstrated. 4 Rapid, reversible and selective tachyphylaxis to 5-HT was demonstrated during perfusion with 5-HT. In hearts desensitized to DMPP by perfusion with DMPP, responses to 5-HT were also reduced. 5 Perfusion of hearts with colchicine inhibited stimulant responses to 5-HT and DMPP but had little effect on responses to noradrenaline or tyramine. 6 Desmethylimipramine enhanced cardiac stimulant responses to noradrenaline and to a lesser extent, those to 5-HT and DMPP. Responses to tyramine were consistently inhibited by desmethylimipramine. 7 Tetrodotoxin abolished responses of the heart to electrical nerve stimulation but left responses to noradrenaline, 5-HT and DMPP unaffected. 8 5-HT, tyramine and DMPP evoked 3H-release from hearts whose neuronal noradrenaline stores had been labelled by perfusion with [3H]-(-)-noradrenaline. The pattern of release evoked by 5-HT was similar to that of DMPP but differed from that of tyramine. 9 Reducing the calcium concentration in the Tyrode solution from 3.6 to 0.2 mEq/1 did not affect 3H-overflow after tyramine but greatly inhibited that evoked by 5-HT and DMPP. 10 The results confirm that the stimulatn effects of 5-HT on the rabbit isolated heart are the result of noradrenaline release. They further suggest that the site of the release is the terminal sympathetic nerve network. The mechanism of release shows more similarities to that of DMPP (calcium-dependent depolarization and exocytosis) than to that of tyramine (neuronal uptake and stoichiometric displacement).
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Fozard JR,Mwaluko GMdoi
10.1111/j.1476-5381.1976.tb07661.xsubject
Has Abstractpub_date
1976-05-01 00:00:00pages
115-25issue
1eissn
0007-1188issn
1476-5381journal_volume
57pub_type
杂志文章abstract::1 Groups of mice were pretreated with the 5-hydroxytryptamine (5-HT) depletors, fenfluramine or p-chlorophenylalanine (PCPA), followed by pethidine or morphine. 2 Fenfluramine alone produced a short lasting analgesia but PCPA was without any effect. 3 Pethidine and morphine both increased hot plate reaction times meas...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1982.tb09177.x
更新日期:1982-04-01 00:00:00
abstract::1. The cyclic nucleotide phosphodiesterase (PDE) of guinea-pig eosinophils was partially characterized and the effects of selective inhibitors of PDE isoenzymes upon opsonized zymosan (OZ)-stimulated respiratory burst were studied. 2. PDE activity in eosinophil lysates appeared to be membrane-associated, displayed sub...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1991.tb09790.x
更新日期:1991-06-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Emerging evidence indicates that hypertension is mediated by immune mechanisms. We hypothesized that exposure to Porphyromonas gingivalis antigens, commonly encountered in periodontal disease, can enhance immune activation in hypertension and exacerbate the elevation in BP, vascular inflammation ...
journal_title:British journal of pharmacology
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更新日期:2019-06-01 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:BACKGROUND AND PURPOSE:Inhibitors of histone deacetylase (HDAC) are emerging as a promising class of anti-cancer drugs, but a generic deregulation of transcription in neoplastic cells cannot fully explain their therapeutic effects. In this study we evaluated alternative molecular mechanisms by which HDAC inhibitors cou...
journal_title:British journal of pharmacology
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更新日期:2008-02-01 00:00:00
abstract::Oxidized low density lipoproteins (oxLDL) are thought to play a major role in atherosclerosis. OxLDL act in part through alteration of intracellular signalling pathways in cells of the vascular wall. We recently reported that the EGF receptor (EGFR) signalling pathway is activated by lipid peroxidation products (among...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703981
更新日期:2001-04-01 00:00:00
abstract::1 Tegaserod (Zelnorm) is a potent 5-hydroxytryptamine4 (5-HT4) receptor agonist with clinical efficacy in disorders associated with reduced gastrointestinal motility and transit. The present study investigated the interaction of tegaserod with 5-HT2 receptors, and compared its potency in this respect to its 5-HT4 rece...
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pub_type: 杂志文章
doi:10.1038/sj.bjp.0705929
更新日期:2004-11-01 00:00:00
abstract::Ivabradine has proven therapeutic efficacy for cardiac ischaemia and, until proved otherwise, is a very specific inhibitor of the cardiac sinoatrial node I(f) current. In the current issue of the British Journal of Pharmacology, Drouin et al. demonstrated that chronic treatment of the human apoB-100 transgene dyslipid...
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pub_type: 杂志文章
doi:10.1038/bjp.2008.168
更新日期:2008-06-01 00:00:00
abstract::1. A single i.p. injection of bacterial endotoxin in rats (3.5 mg kg-1) caused lung injury assessed as changes in lung dry:wet weight ratio and leukopaenia over the subsequent 28 h. 2. This treatment also slowed the efflux of 14C from [14C]-prostaglandin E2 (PGE2), i.e., increased t1/2 and increased the survival of PG...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1988.tb11485.x
更新日期:1988-04-01 00:00:00
abstract::In this issue of the BJP, Green et al. suggest that animal data could not be used to predict the adverse effects of 3,4-methylenedioxymethamphetamine (MDMA) in humans and that MDMA did not produce 5-HT neurotoxicity in the human brain. This proposal was, however, not accompanied by a review of the empirical evidence i...
journal_title:British journal of pharmacology
pub_type: 评论,杂志文章
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更新日期:2012-07-01 00:00:00
abstract::1. The receptor for glucagon-like peptide-1 (GLP-1) can be activated by both its physiological hormone and a peptide discovered in the venom of the Gila Monster, exendin-4, which shows promise as an antidiabetic agent. 2. Exendin-4 displays receptor-binding properties not observed for GLP-1. Firstly, exendin-4 can be ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705453
更新日期:2003-09-01 00:00:00
abstract::1. TRPM8 (CMR1) is a Ca(2+)-permeable channel, which can be activated by low temperatures, menthol, eucalyptol and icilin. It belongs to the transient receptor potential (TRP) family, and therefore is related to vanilloid receptor type-1 (VR1, TRPV1). We tested whether substances which are structurally related to ment...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705652
更新日期:2004-02-01 00:00:00
abstract::1. Adenosine 5'-triphosphate (ATP) is known to augment cardiac contractile activity and cause an increase in intracellular Ca(2+) concentration ([Ca(2+)](i)) in isolated cardiomyocytes. However, no information regarding the ATP-mediated signal transduction in the myocardium in congestive heart failure (CHF) is availab...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705867
更新日期:2005-01-01 00:00:00
abstract::1. In the zymosan rat air pouch model of inflammation we have assessed the time dependence of phospholipase A2 (PLA2) accumulation in the inflammatory exudates as well as cell migration, myeloperoxidase activity, prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) levels. 2. A significant increase in PLA2 activity was d...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb15353.x
更新日期:1996-04-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Sepsis is a systemic inflammatory response accompanied by excessive production of inflammatory cytokines and cardiovascular dysfunction. Importantly, macrophage-derived pro-inflammatory agents play a key role in cardiovascular impairment in sepsis. Here we have investigated the effects of trimeta...
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doi:10.1111/bph.13386
更新日期:2016-02-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.12692
更新日期:2015-01-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1992.tb14233.x
更新日期:1992-01-01 00:00:00
abstract::1 The activity pattern of analogues of the enkephalins was determined in four parallel assays, the inhibition of the electrically evoked contraction of the guinea-pig ileum and mouse vas deferens at 36 degrees C and the inhibition of [(3)H]-naltrexone and [(3)H]-leucine-enkephalin binding at 0 to 4 degrees C in homoge...
journal_title:British journal of pharmacology
pub_type: 杂志文章
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更新日期:1980-02-01 00:00:00
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pub_type: 杂志文章
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更新日期:1994-08-01 00:00:00
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更新日期:1980-07-01 00:00:00
abstract::1. To determine the possible role of Ca(2+)-activated K+ (KCa) channels in the regulation of resting tone of arteries from spontaneously hypertensive rats (SHR), the effects of agents which interact with these channels on tension and 86Rb efflux were compared in endothelium-denuded strips of carotid, femoral and mesen...
journal_title:British journal of pharmacology
pub_type: 杂志文章
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更新日期:1993-01-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1987.tb11256.x
更新日期:1987-07-01 00:00:00
abstract::1. A wide panel of compounds acting on beta-adrenoceptors active either in mammalian heart or in rodent digestive tract and adipose tissues, were investigated for their effects on Chinese hamster ovary cells transfected with the human or murine beta 3-adrenoceptor gene. 2. The beta 3-agonists, bucindolol, CGP 12177A a...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1994.tb13167.x
更新日期:1994-07-01 00:00:00
abstract::Despite progression in anticancer drug development and improvements in the clinical utilization of therapies, current treatment regimes are still dependent upon the use of systemic antiproliferative cytotoxic agents. Although these agents are unquestionably potent, their efficacy is limited by toxicity towards 'normal...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1038/sj.bjp.0707657
更新日期:2008-04-01 00:00:00
abstract::1. Depolarization of rat cerebral cortical slices, prelabelled with [3H]-histidine, in high potassium (40 mM KCl) medium stimulated the release of [3H]-histamine. The K+-evoked release of [3H]-histamine was attenuated by incubation in calcium-free medium and prevented by prior incubation of brain slices with the selec...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1988.tb11758.x
更新日期:1988-12-01 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.0707607
更新日期:2008-03-01 00:00:00
abstract::Rodent models of chronic pain may elucidate pathophysiological mechanisms and identify potential drug targets, but whether they predict clinical efficacy of novel compounds is controversial. Several potential analgesics have failed in clinical trials, in spite of strong animal modelling support for efficacy, but there...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1476-5381.2011.01300.x
更新日期:2011-10-01 00:00:00
abstract::1. Rat spinal cord neurones grown in tissue culture were used to examine the electrophysiological effects of the neurokin in (NK)-selective agonists (pGlu6, Pro9) substance P(6-11) (septide; NK1, 10(-6)M) and (pGlu5, MePhe8, MeGly9)SP(1-7) (DiMe-C7; NK3, 10(-6)M). In addition, the effect of the neurokinin antagonist (...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1989.tb14621.x
更新日期:1989-11-01 00:00:00
abstract::Substance P and substance K (neurokinin A) (dose range: 0.08-80 nmol kg-1) were tested for their effects on gastrointestinal propulsion in the rat. The peptides were given by intraperitoneal injection concurrently with the intragastric administration of a test meal containing charcoal and 51Cr. Examination 3 min after...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1985.tb09462.x
更新日期:1985-09-01 00:00:00
abstract::1. The mechanisms of action of semotiadil fumarate, a novel Ca2+ antagonist, were examined by measuring the cytosolic Ca2+ level ([Ca2+]i) and force of contraction in porcine coronary arteries, and by determining [3H]-pyrilamine binding to bovine cerebellar membranes. 2. Semotiadil or verapamil (0.1 and 1 microM) inhi...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb13345.x
更新日期:1995-03-01 00:00:00