Abstract：
BACKGROUND AND PURPOSE:Selective and potent antagonists for the β(2) -adrenoceptor are potentially interesting as experimental and clinical tools, and we sought to identify novel ligands with this pharmacology. EXPERIMENTAL APPROACH:A range of pharmacological assays was used to assess potency, affinity, selectivity (β(2) -adrenoceptor vs. β(1) -adrenoceptor) and efficacy. KEY RESULTS:Ten novel compounds were identified but none had as high affinity as the prototypical β(2) -adrenoceptor blocker ICI-118,551, although one of the novel compounds was more selective for β(2) -adrenoceptors. Most of the ligands were inverse agonists for β(2) -adrenoceptor-cAMP signalling, although one (5217377) was a partial agonist and another a neutral antagonist (7929193). None of the ligands were efficacious with regard to β(2) -adrenoceptor-β-arrestin signalling. The (2S,3S) enantiomers were identified as the most active, although unusually the racemates were the most selective for the β(2) -adrenoceptors. This was taken as evidence for some unusual enantiospecific behaviour. CONCLUSIONS AND IMPLICATIONS:In terms of improving on the pharmacology of the ligand ICI-118,551, one of the compounds was more selective (racemic JB-175), while one was a neutral antagonist (7929193), although none had as high an affinity. The results substantiate the notion that β-blockers do more than simply inhibit receptor activation, and differences between the ligands could provide useful tools to investigate receptor biology.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Hothersall JD,Black J,Caddick S,Vinter JG,Tinker A,Baker JRdoi
10.1111/j.1476-5381.2011.01269.xsubject
Has Abstractpub_date
2011-09-01 00:00:00pages
317-31issue
2eissn
0007-1188issn
1476-5381journal_volume
164pub_type
杂志文章abstract：BACKGROUND AND PURPOSE:Interstitial lung disease accounts for a group of chronic and progressive disorders associated with severe pulmonary vascular remodelling, peripheral vascular rarefaction and fibrosis, thus limiting lung function. We have previously shown that Akt is necessary for myofibroblast differentiation, a...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.13203
更新日期：2015-08-01 00:00:00
abstract：:In helical strips cut from the small mesenteric artery of guinea-pig (GPSMA) (0.3-0.6 mm o.d.) relaxations induced by substance P were more susceptible to damage of the endothelium by rubbing than were relaxations evoked by carbachol. Relaxations induced by 2-nicotin-amidoethyl nitrate (SG75) were unaffected by this p...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1986.tb14589.x
更新日期：1986-04-01 00:00:00
abstract：:Osteoarthritis (OA) is the most common disease of joints, which are complex organs where cartilage, bone and synovium cooperate to allow a range of movements. During progression of the disease, the function of all three main components is jeopardized. Nevertheless, the involvement of each tissue in OA development is s...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.14204
更新日期：2019-05-01 00:00:00
abstract：:1. Derivatization of nonsteroidal anti-inflammatory drugs, such that they release nitric oxide (NO) in small amounts, has been shown to significantly increase their anti-inflammatory activity and analgesic potency. In this study, we compared the anti-inflammatory potency of prednisolone to a nitric oxide-releasing der...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0705324
更新日期：2003-07-01 00:00:00
abstract：:1. Our study was aimed at investigating the duration of the bronchodilator action of the antimuscarinc drug glycopyrrolate compared to tiotropium and ipratropium. In the guinea-pig isolated trachea, the time (t1/2) necessary for a contractile response to carbachol (0.3 microM) to return to 50% recovery after washout o...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0706724
更新日期：2006-06-01 00:00:00
abstract：:The concentration in rat striatum of the meta and para isomers of tyramine and alpha-methyltyramine, after the administration of (+)-amphetamine, alpha-methyl-p-tyrosine (AMPT) and alpha-methylphenylalanine (AMPA) has been determined using chemical ionization gas chromatography mass spectrometry (c.i.g.c.m.s.). Twenty...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1983.tb10035.x
更新日期：1983-10-01 00:00:00
abstract：:1. The actions of etorphine, morphine and diprenorphine were investigated on neurones of the cerebral cortex and spinal cord of rats anaesthetized with pentobarbitone.2. In the cerebral cortex, intravenous etorphine increased the latency of the primary evoked response to a peripheral nerve stimulus and suppressed the ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1972.tb06865.x
更新日期：1972-10-01 00:00:00
abstract：:The vanilloid receptor (VR1) is a ligand-gated ion channel, which plays an important role in nociceptive processing. Therefore, a pharmacological characterization of the recently cloned rat VR1 (rVR1) was undertaken. HEK293 cells stable expressing rVR1 (rVR1-HEK293) were loaded with Fluo-3AM and then incubated at 25 d...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0703390
更新日期：2000-06-01 00:00:00
abstract：:(1) Increased oxidative stress plays a significant role in the etiology of cardiovascular disease. Lipid peroxidation, initiated in the presence of hydroxy radicals resulting in the production of malondialdehyde, directly produces oxidative stress. This study was designed to examine the direct impact of malondialdehyd...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0705384
更新日期：2003-08-01 00:00:00
abstract：:1. The effects of suramin on an adenosine 5'-triphosphate (ATP)-activated inward current were investigated in PC12 phaeochromocytoma cells with whole-cell voltage-clamp techniques. 2. Suramin (30 to 300 microM) inhibited the ATP-activated current in a dose-dependent manner. The inhibitory effects were reversible and c...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1990.tb12117.x
更新日期：1990-09-01 00:00:00
abstract：:1. Muscarinic receptors present in the human astrocytoma cell line 1321 N1 were characterized in radioligand binding studies and in functional studies of carbachol-stimulated phosphatidylinositol (PI) turnover. 2. In radioligand binding studies the muscarinic receptor in intact cells could be labelled using [3H]-N-met...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1989.tb11813.x
更新日期：1989-02-01 00:00:00
abstract：:1. The effects of 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB) were investigated on evoked and spontaneous currents in freshly-isolated cells from the rat portal vein by use of conventional whole-cell recording and perforated-patch techniques. 2. At a holding potential of -60 mV in potassium-free, caesium-conta...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1996.tb15171.x
更新日期：1996-01-01 00:00:00
abstract：:Chemotherapy-induced immune-suppression is a common, but potential detrimental, adverse reaction in patients undergoing treatment for cancer and strategies with capacity to boost the immune cell populations are needed. Physical exercise training is a potent regulator of immune cell viability and function and may serve...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.15141
更新日期：2020-05-25 00:00:00
abstract：:1. The effects of methylflavonolamine hydrochloride (4'-methyl-7-(2-hydroxy-3-isopropylamino-propoxy)-flavone hydrochloride, MFA) were investigated and compared with verapamil and papaverine on rabbit isolated aortic strips, which were contracted by noradrenaline, calcium and potassium. 2. Pre-incubation for 25 min wi...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1988.tb11637.x
更新日期：1988-08-01 00:00:00
abstract：:1 We investigated the peripheral haemodynamic effects of human alpha-calcitonin gene-related peptide (CGRP) following administration of endothelin-1 or NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide production, in conscious, chronically-instrumented, Long Evans rats. 2 Infusion of endothelin-1...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1991.tb12333.x
更新日期：1991-05-01 00:00:00
abstract：:1. The possible mechanisms of action of the inhibitory effect of gomisin C on the respiratory burst of rat neutrophils in vitro was investigated. 2. The peptide formyl-Met-Leu-Phe (FMLP) induced superoxide anion (O2-) formation and O2 consumption, which was inhibited by gomisin C in a concentration-dependent manner (I...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1994.tb17084.x
更新日期：1994-11-01 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:Normal pregnancy is associated with decreased vascular resistance and increased release of vasodilators. Endothelin-1 (ET-1) causes vasoconstriction via endothelin receptor type A (ET(A)R), but could activate ET(B)R in the endothelium and release vasodilator substances. However, the roles of ET(B...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.12225
更新日期：2013-07-01 00:00:00
abstract：BACKGROUND AND PURPOSE:AZ11645373 and N-{2-methyl-5-[(1R, 5S)-9-oxa-3,7-diazabicyclo[3.3.1]non-3-ylcarbonyl]phenyl}-2-tricyclo[3.3.1.13,7]dec-1-ylacetamide hydrochloride (compound-22) are recently described P2X(7) receptor antagonists. In this study we have further characterized these compounds to determine their mecha...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2009.00135.x
更新日期：2009-04-01 00:00:00
abstract：:The antioestrogen, tamoxifen, blocks volume-regulated chloride channels and reduces transparency in bovine lenses maintained in vitro. In contrast to tamoxifen, the steroidal antioestrogen, ICI 182780, did not block volume-regulated chloride currents in three cultured cell lines and required 10 fold higher concentrati...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1995.tb16622.x
更新日期：1995-08-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Acute activation of κ opioid (KOP) receptors results in anticocaine-like effects, but adverse effects, such as dysphoria, aversion, sedation and depression, limit their clinical development. Salvinorin A, isolated from the plant Salvia divinorum, and its semi-synthetic analogues have been shown t...
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
abstract：:1. The present study was designed to characterize the nociceptive response induced by protein kinase C (PKC) peripheral activation and to investigate if this biochemical event is important for the nociceptive response induced by formaldehyde, and bradykinin (BK). 2. Intraplantar injection of phorbol-12,13-didecanoate ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0704434
更新日期：2002-01-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Tobacco smoke represents a relevant risk factor for coronary heart disease (CHD). Although peroxisome proliferator-activated receptor (PPAR)gamma activation reduces inflammation and atherosclerosis, expression of PPARgamma in cells and its modulation by smoking are poorly investigated. We previou...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2009.00442.x
更新日期：2009-11-01 00:00:00
abstract：:The pharmacological properties of fatty acid amidohydrolase (FAAH) were investigated in brains of 35-day-old chickens, since nothing is known about the enzyme in avian species. FAAH activity towards both [(3)H]-palmitoylethanolamide (PEA) [K(M)=1.5 microM] and [(3)H]-anandamide (AEA) [K(M)=5.4 microM] was demonstrated...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0703569
更新日期：2000-10-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Imiquimod is an immunomodulator approved for the treatment of basal cell carcinoma and has adverse side effects, including taste disturbances. Paracrine transmission, representing cell-cell communication within taste buds, has the potential to shape the final signals that taste buds transmit to t...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.13567
更新日期：2016-11-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Orally administered withanoside IV (a compound isolated from the roots of Withania somnifera) improved memory deficits in mice with a model of Alzheimer's disease induced by the amyloid peptide Abeta(25-35). Sominone, an aglycone of withanoside IV, was identified as an active metabolite after ora...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2009.00313.x
更新日期：2009-08-01 00:00:00
abstract：:1. Rat mesenteric (approximately 250 microns) were set up in a single-channel isometric myograph designed to allow with 6 microM fura-2AM for 2 h and simultaneous recordings of neurogenic contraction (force) and intracellular calcium [Ca2+]i were obtained. In other experiments, arteries were loaded with 1 microCi ml-1...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701337
更新日期：1997-09-01 00:00:00
abstract：:We investigated the ability of the cannabinoid agonists CP55,940 (CB(1)/CB(2)) and anandamide (endogenous cannabinoid) to modulate electrical field stimulation (EFS)-induced acetylcholine (ACh) release from parasympathetic nerve terminals innervating guinea-pig trachea. We assessed whether modulation of transmitter re...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0703497
更新日期：2000-08-01 00:00:00
abstract：:1. The purpose of the present study was to develop an experimental strategy for the quantification of the cardiovascular effects of non-selective adenosine receptor ligands at the adenosine A1 and A2a receptor in vivo. 2-Chloroadenosine (CADO) was used as a model compound. 2. Three groups of normotensive conscious rat...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1996.tb15412.x
更新日期：1996-05-01 00:00:00
abstract：:1. The role of endogenous ADP in platelet aggregation in vivo remains unclear due to the lack of suitable P2T-antagonist probes. This paper describes the potency, selectivity and specificity of the novel P 2T-purinoceptor antagonist, FPL 67085 (2-propylthio-D-beta,gamma-dichloromethylene ATP) both in vitro and in the ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1995.tb15925.x
更新日期：1995-07-01 00:00:00
