Abstract：
:1. The irreversible opioid receptor antagonist beta-chlornaltrexamine (beta-CNA) has been shown previously to have agonist activity in the guinea-pig ileum preparation. However, the receptor type or types mediating this effect have not been established. 2. In this study, the agonism of beta-CNA was investigated by use of the competitive antagonist 16-methylcyprenorphine (RX8008M). Non-cumulative concentration-effect curves for beta-CNA were displaced in a non-parallel fashion indicating that the agonism was mediated by both mu- and kappa-receptors. 3. In principle, expression of agonism by an irreversible receptor antagonist could compromise its use in estimating agonist dissociation constants (pKAs) due to desensitization operating in addition to receptor inactivation. For kappa-receptors, this possibility was checked by use of ethylketocyclazocine (EKC) to mimic the agonist effects of beta-CNA and test whether subsequent EKC concentration-effect curves were displaced. For mu-receptors it was necessary to perform more involved experiments in which [D-Ala2, MePhe4, Gly-ol5]enkephalin (DAGOL) was used as a standard agonist and its pKA was estimated under different conditions of beta-CNA incubation. 4. These analyses indicated that neither the mu- nor the kappa-receptor-mediated agonism of beta-CNA was associated with appreciable receptor desensitization. In turn it was concluded that the usefulness of beta-CNA as a pharmacological tool for the estimation of mu- and kappa-opioid receptor agonist dissociation constants is not compromised by the agonist effects that the compound demonstrates at these receptors.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Leff P,Dougall IGdoi
10.1111/j.1476-5381.1988.tb16569.xsubject
Has Abstractpub_date
1988-09-01 00:00:00pages
234-40issue
1eissn
0007-1188issn
1476-5381journal_volume
95pub_type
杂志文章abstract：BACKGROUND AND PURPOSE:The anti-cancer agent [Arg(6), D-Trp(7,9), N(me)Phe(8)]-substance P (6-11) (SP-G) modulates gastrin releasing peptide (GRP) and arginine vasopressin signalling in small cell lung cancer cells leading to growth arrest and apoptosis. We have shown that SP-G acts as a biased agonist at GRP receptors...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2008.00003.x
更新日期：2009-01-01 00:00:00
abstract：:1. We investigated the potent 5-hydroxytryptamine (5-HT)-mediated vasorelaxation of the sheep pulmonary vein. Here we present evidence that this response is due to activation of 5-HT4 receptors. 2. 5-HT (1-1000 nM) caused concentration-dependent, maintained relaxations (pEC50 = 8.4 +/- 0.1) of isolated rings of sheep ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1992.tb12788.x
更新日期：1992-10-01 00:00:00
abstract：BACKGROUND AND PURPOSE:The two longest C-termini of the purinergic P2X receptors occur in the P2X2 and P2X7 receptors and are thought to interact with multiple cytoplasmic proteins, among which are members of the cytoskeleton, including microtubules. In this work we asked whether disrupting the microtubule cytoskeleton...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2011.01254.x
更新日期：2011-07-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Tumour cell-induced platelet aggregation (TCIPA) facilitates cancer cell invasion, angiogenesis and the formation of metastatic foci. TCIPA can be modulated by pharmacological inhibitors of MMP-2 and ADP; however, the COX inhibitor aspirin did not prevent TCIPA. In this study, we have tested the ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2011.01794.x
更新日期：2012-06-01 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：BACKGROUND AND PURPOSE:Betulinic acid (BA) is a naturally occurring triterpenoid widely distributed throughout the plant kingdom. We previously reported that BA inhibits lipopolysaccharide (LPS)-induced interleukin-6 production through modulation of nuclear factor κB (NF-κB) in human peripheral blood mononuclear cells ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2010.01112.x
更新日期：2011-03-01 00:00:00
abstract：:1. A number of superoxide dismutase (SOD) mimetics were examined both biochemically for their ability to inhibit the superoxide-catalyzed reduction of cytochrome c and nitro blue tetrazolium, and functionally for their ability to mimic authentic Cu/Zn SOD in restoring nitrergic neurotransmission in bovine retractor pe...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701809
更新日期：1998-05-01 00:00:00
abstract：:1. The effect on systemic haemodynamics of BQ-123, a selective endothelin A (ETA) receptor antagonist, was investigated in healthy men by giving, on separate occasions, ascending intravenous doses of 100, 300, 1000 and 3000 nmol min(-1) BQ-123, each for 15 min, in a randomized, placebo-controlled, double-blind study. ...
journal_title：British journal of pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1038/sj.bjp.0704304
更新日期：2001-10-01 00:00:00
abstract：:1. The aim of the present study was to examine whether ramipril induces delayed myocardial protection against free radical injuries ex vivo and to determine the possible role of the bradykinin B2-nitric oxide (NO) pathway, prostaglandins(PGs) and protein synthesis in this delayed adaptive response. 2. Rats were pretre...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702089
更新日期：1998-10-01 00:00:00
abstract：:1. In the conscious rat, three tachykinin NK3 receptor antagonists, namely SR142801 ((S)-(N)-(1-(3-(1-benzoyl-3-(3,4-dichlorophenyl)piperidin-3-yl)pro pyl)-4-phenylpiperidin-4-yl)-N-methylacetamide), R820 (3-indolylcarbonyl-Hyp-Phg-N(Me)-Bzl) and R486 (H-Asp-Ser-Phe-Trp-beta-Ala-Leu-Met-NH2) were assessed against the ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701435
更新日期：1997-10-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Non-invasive in vivo imaging of cannabinoid CB2 receptors using PET is pursued to study neuroinflammation. The purpose of this study is to evaluate the in vivo binding specificity of [18 F]MA3, a CB2 receptor agonist, in a rat model with local overexpression of human (h) CB2 receptors. METHODS:[...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.14564
更新日期：2019-05-01 00:00:00
abstract：:The arterial endothelium critically contributes to blood pressure control by releasing vasodilating autacoids such as nitric oxide, prostacyclin and a third factor or pathway termed 'endothelium-derived hyperpolarizing factor' (EDHF). The nature of EDHF and EDHF-signalling pathways is not fully understood yet. However...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/j.1476-5381.2009.00132.x
更新日期：2009-06-01 00:00:00
abstract：:1. We have characterized the human smooth muscle endothelin converting enzyme (ECE) present in the media of the endothelium-denuded human umbilical vein preparation. 2. Endothelin-1 (ET-1) and ET-2 were potent constrictors of umbilical vein with EC50 values of 9.2 nM and 29.6 nM, respectively. ET-1 was at least 30 tim...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701564
更新日期：1997-12-01 00:00:00
abstract：:1. Morphine, oxotremorine and physostigmine showed antinociceptive activity in mice using the hot plate reaction time test.2. The action of morphine, but not that of oxotremorine, was antagonized by naloxone and by nalorphine, whereas the effect of physostigmine was unaffected by naloxone and increased by nalorphine.3...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1971.tb07205.x
更新日期：1971-12-01 00:00:00
abstract：BACKGROUND:Dimebolin (latrepirdine), a compound with multiple potential drug targets, is being evaluated in clinical trials for the treatment of Alzheimer's disease (AD) and preliminary results suggest it can slow the disease process. There is also evidence that dimebolin directly improves aspects of cognition. Here we...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2011.01432.x
更新日期：2011-10-01 00:00:00
abstract：:1. Repeated allergen challenge has been shown to increase the role of Rho-kinase in airway smooth muscle (ASM) contraction. We considered the possibility that active allergic sensitization by itself, that is, without subsequent allergen exposure, could be sufficient to enhance Rho-kinase-mediated ASM contraction. 2. G...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0705903
更新日期：2004-10-01 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：:Halothane has many effects on the resting membrane potential (V(m)) of excitable cells and exerts numerous effects on skeletal muscle one of which is the enhancement of Ca(2+) release by the sarcoplasmic reticulum (SR) resulting in a sustained contracture. The aim of this study was to analyse the effects of clinical d...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0703330
更新日期：2000-06-01 00:00:00
abstract：:In electrophysiological measurements the beta-carboline ethyl 6-benzyloxy-beta-carboline-3-carboxylate (ZK 91085) acts as a positive allosteric modulator on rat recombinant alpha1beta2gamma2 GABA(A) receptors and binds with high affinity (IC50-1.5 nM) to the [3H]-flunitrazepam site. Flumazenil was able to partially co...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702639
更新日期：1999-07-01 00:00:00
abstract：BACKGROUND AND PURPOSE:alpha5IA (3-(5-methylisoxazol-3-yl)-6-[(1-methyl-1,2,3-triazol-4-yl)methyloxy]-1,2,4-triazolo[3,4-a]phthalazine) is a triazolophthalazine with subnanomolar affinity for alpha1-, alpha2-, alpha3- and alpha5-containing GABA(A) receptors. Here we have evaluated the relationship between plasma alpha5...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2009.00216.x
更新日期：2009-07-01 00:00:00
abstract：:1. We have investigated the effect of phorbol esters and the down-regulation of protein kinase C on contraction of guinea-pig ileum longitudinal smooth muscle to carbachol and high K+. 2. Phorbol 12,13-dibutyrate (PDBu) enhanced the phasic component and inhibited or enhanced, respectively, the tonic component of contr...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1989.tb14607.x
更新日期：1989-11-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Partial agonists selective for α4β2 nicotinic ACh receptors have been developed for smoking cessation as they induce weak activation of native α4β2* receptors and inhibit effect of nicotine. However, it is unclear whether at brain functions there is an existence of receptor reserve that allows we...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2011.01628.x
更新日期：2012-02-01 00:00:00
abstract：:1. We previously reported that substance P and insulin-like growth factor-1 (IGF-1) synergistically stimulate corneal epithelial wound healing in vitro and in vivo. We wished to identify which portion of the amino acid sequence of substance P might be responsible for this synergism. 2. Corneal epithelial migration was...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702550
更新日期：1999-05-01 00:00:00
abstract：:1. Comparison of the rank order of potency of the natural prostanoids prostaglandin E2 (PGE2), PGD2, PGF2 alpha and carbaprostacyclin in stimulating cyclic AMP in Jurkat cells is consistent with the presence of an EP receptor. 2. Lack of responsiveness to the EP1/EP3 selective agonist, sulprostone, and the EP2 agonist...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1995.tb15030.x
更新日期：1995-08-01 00:00:00
abstract：:1. The inhibitory effect of caffeine on the calcium channel current was investigated in cultured myometrial cells isolated from pregnant rats. 2. Caffeine inhibited the calcium channel current elicited from a holding potential of -70 mV in a concentration-dependent manner. The IC50 was estimated to be 35 mM. 3. The ca...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1989.tb12622.x
更新日期：1989-10-01 00:00:00
abstract：:The consumption of green tea (Camellia sinensis) has been shown to have many physiological and pharmacological health benefits. In the past two decades several studies have reported that epigallocatechin-3-gallate (EGCG), the main constituent of green tea, has anti-infective properties. Antiviral activities of EGCG wi...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.12009
更新日期：2013-03-01 00:00:00
abstract：:1. Inducible NO synthase (iNOS) expression and activity were measured in the mouse macrophage cell line J774 after exposure to bacterial lipopolysaccharide (LPS) with or without interferon-gamma (IFN-gamma). 2. Inhibition of NOS activity by concomitant N(G)-monomethyl-L-arginine (L-NMMA) treatment further increased iN...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0703838
更新日期：2001-01-01 00:00:00
abstract：:1. We have investigated the mechanism of smooth muscle contraction evoked by activation of 5-HT1-like receptors in dog isolated saphenous vein. 2. In the presence of the 5-HT2 receptor antagonist, ritanserin (0.1 microM), concentration-effect curves (10 nM-300 microM) for 5-hydroxytryptamine (5-HT)-induced smooth musc...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1992.tb09026.x
更新日期：1992-03-01 00:00:00
abstract：:1. Intracellular microelectrode recording techniques were performed on mouse spinal cord and cerebral hemisphere neurones grown in primary dissociated cell culture. The effects of several anxiolytics applied by local pressure ejection on responses to gamma-aminobutyric acid (GABA) evoked by iontophoresis were investig...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1988.tb16554.x
更新日期：1988-09-01 00:00:00
abstract：:1. Noradrenaline 1 microM induced a contractile response in rat isolated aorta in the presence or in the absence of extracellular Ca2+ with depletion of intracellular Ca2+ stores. Thereafter, during incubation in the presence of Ca2+, an increase in the resting tone was observed. Such a contractile response did not oc...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1993.tb13892.x
更新日期：1993-10-01 00:00:00
