Abstract:
:The pharmacological properties of endothelin receptors (ETR) were investigated in guinea-pig bronchus by comparing binding and functional results. In binding assays, both the ET(B) agonists, endothelin-3 (ET-3) and N-suc-[Glu9,Ala11,15]ET-1(8-21) (IRL 1620), and the antagonist, N-cis-2,6-dimethylpiperidinocarbonyl-L-gamma-methylleucyl-D- 1-methoxycarbonyltryptophanyl-D-norleucine (BQ 788), showed biphasic inhibition curves of [125I]-endothelin-1 (ET-1) binding to bronchus membranes prepared from intact or epithelium-deprived tissue. IRL 1620 did not completely displace specifically [125I]-ET-1 bound to these tissue preparations. In the presence of the ET(A)-selective antagonist, cyclo(-D-Trp-D-Asp-L-Pro-D-Val-L-Leu) (BQ 123, 1 microM), IRL 1620 displacement curves were shallow but a complete inhibition was reached at a concentration of 1 microM. Both curves were better represented by two-site models. In addition, BQ 788 competition curves became monophasic when binding experiments were performed in the presence of 1 microM BQ 123. The non-selective agonist, ET-1, and BQ 123 inhibited [125I]-ET binding to bronchus membranes in dose-dependent fashions with monophasic curves. The contracting activity of IRL 1620 (0.55 nM- 1.6 microM) was tested on multiple-ring bronchial preparations pretreated with peptidase and cyclo-oxygenase inhibitors. BQ 788 shifted IRL1620 concentration-response curves to the right while BQ 123 did not influence bronchial responsiveness. In addition, a potentiation of the maximal response to the agonist was observed in BQ 788 treated bronchial rings. This effect was abolished by tissue pretreatment with Nomega-nitro-L-argininemethylester (L-NAME) or epithelium removal but not by pretreatment with atropine or iberiotoxin. Our results demonstrate that guinea-pig bronchus contains two populations of ET(B) receptors with different affinities for the ET(B)-selective agonist, IRL 1620. One ET(B) receptor population appears to activate bronchial muscle contraction while another on epithelial cells causes muscle relaxation through the release of nitric oxide (NO).
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Mazzoni MR,Breschi MC,Ceccarelli F,Lazzeri N,Giusti L,Nieri P,Lucacchini Adoi
10.1038/sj.bjp.0702672subject
Has Abstractpub_date
1999-07-01 00:00:00pages
1406-14issue
6eissn
0007-1188issn
1476-5381journal_volume
127pub_type
杂志文章abstract:BACKGROUND AND PURPOSE:Histone deacetylase 6 (HDAC6) and silent information regulator 2 (SIRT2) control the dynamics of the microtubule network via their deacetylase activities. Tubulin polymerization promoting protein (TPPP/p25) enhances microtubule acetylation by its direct binding to HDAC6. Our objective was to char...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.12946
更新日期:2015-02-01 00:00:00
abstract::1. Noradrenaline sensitivity and acetylcholine-induced relaxation were investigated in mesenteric resistance arteries from female Wistar rats (220-250 g) following exposure to isotonic supraphysiological glucose solutions (20 and 45 mM, in physiological buffer, 2 h incubation). 2. Arteries incubated in 20 mM glucose d...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1994.tb17064.x
更新日期:1994-11-01 00:00:00
abstract::1 Neuroprotection has been reported after either activation or blockade of the group I metabotropic glutamate receptor subtype 5 (mGluR5). However, some recent evidence suggests that protection provided by mGluR5 antagonists may reflect their ability to inhibit N-methyl-D-aspartate (NMDA) receptor activity. 2 Here, in...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0706219
更新日期:2005-06-01 00:00:00
abstract::1 The activity and pulmonary metabolism of two peptides, 7-homo Pro-bradykinin and 8-homo Phe-bradykinin were studied in isolated systems. 2 Both analogues were about 50-70 times less active than bradykinin on the guinea-pig ileum and 70-160 times less active on isolated strips of cat terminal ileum. 3 The action of b...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1977.tb06985.x
更新日期:1977-01-01 00:00:00
abstract::1. The macroscopic currents induced in cultured rat melanotrophs by exogenous gamma-aminobutyric acid (GABA) were analysed using the patch clamp recording technique. 2. Using various concentrations of intra- and extracellular chloride it was demonstrated that the conductance activated by GABA was chloride selective. S...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1987.tb11359.x
更新日期:1987-11-01 00:00:00
abstract::1. Some hydroxy-, amino-, and methoxy- phenylalkyltrimethylammonium compounds, beta-pyridylmethyl- dimethylamine and pyrrolidine, and beta-pyridylethyltrimethylammonium, were tested on avoidance learning in mice and their effects were compared with those of (-)-nicotine.2. The o- and m- hydroxybenzyl-, o-hydroxyphenet...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1970.tb10372.x
更新日期:1970-07-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Pemphigus and pemphigoid diseases are characterized and caused predominantly by IgG autoantibodies targeting structural proteins of the skin. Their current treatment relies on general and prolonged immunosuppression that causes severe adverse events, including death. Hence, novel safe and more ef...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.14986
更新日期:2020-05-01 00:00:00
abstract::1. The goal of this study was to investigate the effects of the delayed pharmacological preconditioning produced by an adenosine A(1)-receptor agonist (A(1)-DPC) against ventricular arrhythmias induced by ischaemia and reperfusion, compared to those of ischaemia-induced delayed preconditioning (I-DPC). 2. Eighty-nine ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704407
更新日期:2001-12-01 00:00:00
abstract::Two prostaglandin endoperoxide analogues, EP 035 and EP 157, behave as specific thromboxane receptor antagonists on isolated smooth muscle preparations such as rabbit aorta, dog saphenous vein and guinea-pig trachea. However, in human platelet-rich plasma (PRP) they produce an unsurmountable block of aggregation induc...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1986.tb10196.x
更新日期:1986-03-01 00:00:00
abstract::Ligands targeting GPCRs can be categorized according to their intrinsic efficacy to trigger a specific, receptor-mediated response. A ligand endowed with the same level of efficacy as the endogenous agonist can be classified as a full agonist, whereas a compound that displays greater efficacy, that is, higher receptor...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bph.13278
更新日期:2016-10-01 00:00:00
abstract::1. Adenosine A(1), A(2A), and A(3) receptors (ARs) and extracellular signal-regulated kinase 1/2 (ERK1/2) play a major role in myocardium protection from ischaemic injury. In this study, we have characterized the adenosine receptor subtypes involved in ERK1/2 activation in newborn rat cardiomyocytes. 2. Adenosine (non...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705614
更新日期:2004-01-01 00:00:00
abstract::1. PD 81,723 has been shown to enhance binding of adenosine to A1 receptors by stabilizing G protein-receptor coupling ('allosteric enhancement'). Evidence has been provided that in the perfused hearts and isolated atria PD 81,723 causes a sensitization to adenosine via this mechanism. 2. We have studied the effect of...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701254
更新日期:1997-07-01 00:00:00
abstract::1. The effects of purinergic stimulation on action potential, force of contraction, 86Rb efflux and 45Ca uptake were investigated in guinea-pig left atria. 2. Adenosine exerted a negative inotropic effect which was antagonized by adenosine deaminase but enhanced by dipyridamole. 3. The negative inotropic effect of ade...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1989.tb12577.x
更新日期:1989-08-01 00:00:00
abstract::The presence of functional cannabinoid CB2 receptors in the CNS has provoked considerable controversy over the past few years. Formerly considered as an exclusively peripheral receptor, it is now accepted that it is also present in limited amounts and distinct locations in the brain of several animal species, includin...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1038/sj.bjp.0707505
更新日期:2008-01-01 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::Peroxynitrite, a potent oxidant formed by the reaction of nitric oxide and superoxide causes thymocyte necrosis, in part, via activation of the nuclear enzyme poly(ADP-ribose) synthetase (PARS). The cytotoxic PARS pathway initiated by DNA strand breaks and excessive PARS activation has been shown to deplete cellular e...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702332
更新日期:1999-02-01 00:00:00
abstract::1. In Ca-free solution, the contractile response of guinea-pig taenia caecum to 10(-4) M carbachol was mediated through muscarinic receptors and was reduced time-dependently by desensitization with 10(-4) M carbachol, but not 10(-4) M histamine. On the other hand, the response to 10(-4) M histamine was shown to be med...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1988.tb11600.x
更新日期:1988-07-01 00:00:00
abstract::1. The effect of in vivo desensitization to leukotriene B4 (LTB4) on eosinophil infiltration in response to recombinant C5a was examined in guinea-pig skin. 2. LTB4 (10-300 ng) and C5a (1-10 micrograms) caused a dose-dependent increase in the levels of eosinophil peroxidase activity (a measure of eosinophil infiltrati...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1994.tb16182.x
更新日期:1994-09-01 00:00:00
abstract::1. Vasorelaxant properties of three nitric oxide (NO) donor drugs (glyceryl trinitrate, sodium nitroprusside and spermine NONOate) in mouse aorta (phenylephrine pre-contracted) were compared with those of endothelium-derived NO (generated with acetylcholine), NO free radical (NO*; NO gas solution) and nitroxyl ion (NO...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704269
更新日期:2001-10-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1977.tb06981.x
更新日期:1977-01-01 00:00:00
abstract::1. We investigated how microsomal cytochrome P450 mono-oxygenase (Cyp450 MO) is regulated in cultured porcine aortic endothelial cells. The hypothesis that a Cyp450 MO-derived metabolite links Ca2+ store depletion and Ca2+ entry was studied further. 2. Microsomal Cyp450 MO was monitored fluorometrically by dealkylatio...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701304
更新日期:1997-08-01 00:00:00
abstract::1 Peptide 401, a potent mast cell degranulating factor from bee venom, substantially inhibited the oedema provoked by subplantar injection of carrageenin or intra-articular injection of turpentine in the rat. The ED(50) of 401 was c. 0.1 mg/kg. The anti-inflammatory effect was assessed by measurement of the increased ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1974.tb09613.x
更新日期:1974-03-01 00:00:00
abstract::1. The effect of prolonged anti-hypertensive drug treatment on the blood pressure of conscious spontaneously hypertensive rats (SH-rats), and of age-matched normotensive Sprague-Dawley rats was determined during the development of hypertension in SH-rats and in the early stages of established hypertension. A compariso...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1975.tb07588.x
更新日期:1975-08-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Erectile dysfunction is highly prevalent in diabetic patients and PDE V inhibitors are effective and safe for the treatment of erectile dysfunction in men with diabetes. Therefore, in this study we investigated whether a pharmacokinetic interaction occurs between DA-8159 and metformin, as both dr...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0707680
更新日期:2008-04-01 00:00:00
abstract::1. A murine macrophage cell line, J774, expressed nitric oxide (NO) synthase activity in response to interferon-gamma (IFN-gamma, 10 u ml-1) plus lipopolysaccharide (LPS, 10 ng ml-1). The enzyme activity was first detectable 6 h after incubation, peaked at 12 h and became undetectable after 48 h. 2. The decline in the...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1993.tb12886.x
更新日期:1993-03-01 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 effects of purported prostaglandin synthesis inhibitors on steroid and prostaglandin (E and F) release from trypsin-dispersed cat adrenocortical cells were investigated. 2 Low indomethacin concentrations potentiated adrenocorticotrophin (ACTH)-evoked prostaglandin and steroid release, whereas higher concentratio...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1976.tb07477.x
更新日期:1976-06-01 00:00:00
abstract::1. Bicyclic compounds with potential thymoleptic properties (Lu-compounds) have recently become available, and their effects on the membrane pumps of the central and peripheral monoamine neurones have now been tested and compared with those of the tricyclic antidepressant drugs.2. Biochemical and histochemical in vivo...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1969.tb08299.x
更新日期:1969-05-01 00:00:00
abstract::1 Nine antibiotic compounds in common use were studied to determine their ability to affect intestinal motility in vitro, in the guinea-pig ileum and rabbit colon. 2 Ampicillin, doxycycline, mecillinam and metronidazole were without effect over a concentration range which included typical serum levels found when these...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1981.tb10453.x
更新日期:1981-06-01 00:00:00
abstract::1. Losigamone is a novel anticonvulsant the mechanism of action of which is not known. This study investigated the effect of losigamone on spontaneous, NMDA- and AMPA-induced depolarizations in the cortical wedge preparation of the DBA/2 mouse (which are susceptible to sound-induced seizures) and on endogenous amino a...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701539
更新日期:1997-12-01 00:00:00