Abstract:
:1. This study analyses the receptors mediating the effects of bradykinin (BK) and analogues on neurogenic twitch contractions of the mouse isolated vas deferens evoked, in the presence of captopril (3 microM), by electrical field stimulation with trains of 4 rectangular 0.5 ms pulses of supramaximal strength, delivered at a frequency of 10 Hz every 20 s. 2. BK (0.1-300 nM) induced a graded potentiation of twitches, with an EC50 (geometric mean and 95% confidence limits) of 4.5 nM (1.7-11.6) and an Emax of 315 +/- 19 mg per 10 mg of wet tissue (n = 6). Similar results were obtained in tissues challenged with Lys-BK, [Hyp3]-BK, Met,Lys-BK and the selective B2 receptor agonist [Tyr(Me)8]-BK (0.1-300 nM). 3. The selective B2 receptor antagonists, Hoe 140 (1-10 nM) and NPC 17731 (3-30 nM), caused graded rightward shifts of the curve to BK-induced twitch potentiation, yielding apparent pA2 values of 9.65 +/- 0.09 and 9.08 +/- 0.13, respectively, and Schild plot slopes not different from 1. Both antagonists (100 nM) failed to modify similar twitch potentiations induced by substance P (3 nM) or endothelin-1 (1 nM). Preincubation with the selective B1 receptor antagonist, [Leu8,des-Arg9]-BK (1 microM), increased the potentiating effect of BK on twitches at 30-300 nM. 4. In contrast to BK, the selective B1 receptor agonist, [des-Arg9]-BK (0.3-1000 nM) reduced the amplitude of twitches in a graded fashion, with an IC50 of 13.7 nM (10.4-16.1) and an Imax of 175 +/- 11 mg (n = 4). The twitch depression induced by [des-Arg9]-BK (300 nM) was not affected by Hoe140 (30nM) or NPC 17731 (100nM), but was abolished by the selective B1 receptor antagonist,[Leu8,des-Arg9]-BK (1 microM), which did not modify the twitch inhibitory effect of clonidine (1 nM) or morphine (300 nM).5. In non-stimulated preparations, BK (100 nM) also potentiated, in a Hoe 140-sensitive (10 nM)manner, the contractions induced by ATP (100 microM), but not by noradrenaline (10 microM), whereas[des-Arg9]-BK (300 nM) did not modify the contractions induced by either agonist.6. It is concluded that the mouse vas deferens expresses both B1 and B2 receptors, which modulate sympathetic neurotransmission in opposing ways. Neurogenic contractions are inhibited by stimulation of possibly prejunctional B, receptors, whereas activation of B2 receptors increases twitch contractions,in part by amplifying the responsiveness of the smooth muscle cells to the sympathetic co-transmitter ATP.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Maas J,Rae GA,Huidobro-Toro JP,Calixto JBdoi
10.1111/j.1476-5381.1995.tb13372.xsubject
Has Abstractpub_date
1995-04-01 00:00:00pages
1471-7issue
7eissn
0007-1188issn
1476-5381journal_volume
114pub_type
杂志文章abstract::1. alpha 1-Adrenoceptor subtypes in rabbit thoracic aorta have been examined in binding and functional experiments. 2. [3H]-prazosin bound to two distinct populations of alpha 1-adrenoceptors (pKD,high = 9.94, Rhigh = 79.2 fmol mg-1 protein; pKD,low = 8.59, Rlow = 215 fmol mg-1 protein). Pretreatment with chloroethylc...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1993.tb13507.x
更新日期:1993-04-01 00:00:00
abstract::1. We have determined which cytokines induce and modulate the production of the chemokine interleukin-8 (IL-8) by the human colonic epithelial cell line HT-29. 2. Growth arrested cell cultures were stimulated with the human recombinant cytokines interleukin-1 alpha (IL-1 alpha), tumour necrosis factor-alpha (TNF-alpha...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb15993.x
更新日期:1996-09-01 00:00:00
abstract::1 The mechanism underlying the enhancement by superoxide dismutase (SOD) of endothelium-dependent relaxation was investigated in rabbit mesenteric resistance arteries. 2 SOD (200 U ml(-1)) increased the production of H(2)O(2) in smooth muscle cells (as indicated by the use of an H(2)O(2)-sensitive fluorescent dye). 3 ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705255
更新日期:2003-05-01 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:BACKGROUND AND PURPOSE:Although there are many new specific phosphodiesterase inhibitors with anti-inflammatory activity, none have yet reached the market because of their low therapeutic efficacy. Our study was aimed to evaluate the anti-inflammatory and anti-arthritic effect of an established phosphodiesterase inhibi...
journal_title:British journal of pharmacology
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doi:10.1111/j.1476-5381.2009.00468.x
更新日期:2009-12-01 00:00:00
abstract::Leukotriene B4 (LTB4) is a potent leukocyte chemoattractant, acting on specific receptors, BLT receptors. The aim of this study was to examine the mechanism of action of LTB4 in the guinea-pig lung, using strips of lung parenchyma (GPLP), spirals of trachea (GPT) and bronchus (GPB) and rings of pulmonary artery (GPPA)...
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doi:10.1038/sj.bjp.0705641
更新日期:2004-02-01 00:00:00
abstract::1. alpha 1-Adrenoceptor densities were studied in cardiac membrane preparations from several mammalian species including human failing hearts under identical experiment conditions; the alpha 1-adrenoceptor antagonist, [3H]-prazosin, was used as radioligand. End-stage heart failure (NYHA IV) in human hearts was due to ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1992.tb14484.x
更新日期:1992-09-01 00:00:00
abstract::1. We examined the effects of selective and nonselective cyclo-oxygenase (COX) inhibitors on various functional changes in the rat stomach induced by topical application of taurocholate (TC) and investigated the preferential role of COX isozymes in these responses. 2. Rat stomachs mounted in ex vivo chambers were perf...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701399
更新日期:1997-10-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1989.tb12618.x
更新日期:1989-10-01 00:00:00
abstract::1. The modulation by alpha 2-adrenoceptors of the jaw-opening reflex (digastric electromyographic responses) elicited by orofacial electrical stimulation (OF-JOR) in pentobarbitone anaesthetized rats was investigated. 2. Increasing doses of clonidine (0.1-1000 micrograms kg-1, i.v.) reduced, in a dose-dependent manner...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1994.tb14864.x
更新日期:1994-04-01 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. Capsaicin, the irritant principle of hot peppers, is a vanilloid agonist known to activate the transient receptor potential channel vanilloid subfamily member 1 (VR1), recently reported to be involved in neurodegeneration. The present study investigated the role of VR1 in a model of global cerebral ischemia in gerb...
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pub_type: 杂志文章
doi:10.1038/sj.bjp.0706115
更新日期:2005-03-01 00:00:00
abstract::Cellular electrophysiological effects of membrane lipid peroxidation by t-butyl hydroperoxide (TBH) were studied in the rabbit sinoatrial (SA) node. Superfusion for 1-5 min with 300 microM TBH caused an initial increase and subsequent decrease in the spontaneous firing frequency of the SA node. Voltage clamp experimen...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1989.tb14598.x
更新日期:1989-11-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Proteinase activated receptor 2 (PAR2) is a GPCR associated with inflammation, metabolism and disease. Clues to understanding how to block PAR2 signalling associated with disease without inhibiting PAR2 activation in normal physiology could be provided by studies of biased signalling. EXPERIMENT...
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pub_type: 杂志文章
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更新日期:2014-09-01 00:00:00
abstract::1. The effects of NS 1619, the putative BKCa channel opener, were investigated on rat intact portal veins and on single smooth muscle cells enzymatically separated from the same tissue. 2. Under whole-cell patch clamp conditions with K-rich pipettes, exposure of single cells held at -10 mV to NS 1619 (10-33 microM) in...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1994.tb17171.x
更新日期:1994-12-01 00:00:00
abstract::1 Uniaxial cyclic stretch leads to an upregulation of cyclooxygenase (COX)-2 through increases in the intracellular Ca(2+) concentration via the stretch-activated (SA) channel and following nuclear factor kappa B (NF-kappaB) activation in human fibroblasts. However, the signaling mechanism as to how the elevated Ca(2+...
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pub_type: 杂志文章
doi:10.1038/sj.bjp.0706182
更新日期:2005-06-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2011.01782.x
更新日期:2012-05-01 00:00:00
abstract::1. Previous work from our laboratory has shown that cannabis induces aggressive behaviour in rats that have been deprived of rapid eye movement (REM) sleep. It was suggested that this effect was related to brain catecholamines, with dopamine playing an agonist role and noradrenaline an inhibitory one. The present pape...
journal_title:British journal of pharmacology
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doi:10.1111/j.1476-5381.1977.tb08429.x
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journal_title:British journal of pharmacology
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doi:10.1111/j.1476-5381.1984.tb16442.x
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更新日期:1992-11-01 00:00:00
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journal_title:British journal of pharmacology
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doi:10.1111/j.1476-5381.1991.tb12486.x
更新日期:1991-11-01 00:00:00
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journal_title:British journal of pharmacology
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doi:10.1111/j.1476-5381.1970.tb09900.x
更新日期:1970-08-01 00:00:00
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journal_title:British journal of pharmacology
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更新日期:2009-11-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701310
更新日期:1997-08-01 00:00:00
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pub_type: 杂志文章
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更新日期:2007-09-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1969.tb10582.x
更新日期:1969-10-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704243
更新日期:2001-09-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1990.tb14193.x
更新日期:1990-12-01 00:00:00
abstract::1. Although anti-alpha(4) integrin mAbs reduce eosinophil accumulation in several models of allergic inflammation, it is not clear whether this occurs via a direct action to block eosinophil alpha(4) integrins or indirectly on another cell type. The role of alpha(4) integrins on the accumulation of (111)In-labelled eo...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703857
更新日期:2001-01-01 00:00:00
abstract::The study was undertaken to investigate the 5-HT receptor mediating the inhibitory effect of 5-HT on peristalsis in the guinea-pig isolated ileum. The facilitatory and inhibitory effects were measured as the decrease and increase, respectively, in the intraluminal pressure required to trigger peristalsis. In the prese...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705184
更新日期:2003-04-01 00:00:00