Abstract:
:1. Membranes from rat cerebral cortex, myocardium and extraorbital lacrimal gland were used as sources of M1, M2 and M3 muscarinic acetylcholine receptors respectively and the affinities of seven antagonists for the three subtypes were examined under different experimental conditions. 2. The affinities for the membrane-bound receptors were measured at different ionic strengths and temperatures and compared with those determined on the receptor solubilised in the neutral detergent digitonin or the zwitterionic detergent, CHAPSO. 3. The range of measured affinity constants of a given antagonist for a specific subtype varied from 2 (atropine at M1 receptors) to 1000 (AF-DX 116 at M2 receptors). 4. As a consequence of these changes in affinity, which were dependent on the drug, the subtype and the experimental conditions, both the structure-binding relationships of a given subtype can be markedly changed as well as the selectivity of a drug for the different subtypes. For example it is possible to change the relative affinities of AF-DX 116 and gallamine at membrane-bound M1 receptors from 50:1 to 1:60. 5. Experimental conditions for the observation of high selectivity of pirenzepine, AF-DX 116, gallamine and hexahydrosiladiphenidol for the three subtypes are given. 6. When the receptors are removed from their membrane environment by solubilisation in detergent, antagonist affinities are changed but the subtypes still retain different structure-binding relationships. 7. In general, AF-DX 116 and the allosteric antagonist, gallamine, behave differently from the other antagonists, suggesting that they bind in different ways to muscarinic receptors. Careful attention should therefore be paid to the experimental conditions in binding assays used to assess the affinities and selectivities of new muscarinic antagonists in order to avoid misleading results. 9. The ability to produce enhanced or attenuated affinities and selectivities of antagonists, resulting from the induction of different conformations of the receptor by a variety of physical, chemical or molecular biological perturbations may lead to a better understanding of the structural basis of drug receptor interactions.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Pedder EK,Eveleigh P,Poyner D,Hulme EC,Birdsall NJdoi
10.1111/j.1476-5381.1991.tb09827.xsubject
Has Abstractpub_date
1991-06-01 00:00:00pages
1561-7issue
2eissn
0007-1188issn
1476-5381journal_volume
103pub_type
杂志文章abstract:BACKGROUND AND PURPOSE:In the sensorimotor (SM) and medial prefrontal (mPF) basal ganglia (BG) circuits, the cortical information is transferred to the substantia nigra pars reticulata (SNr) through the hyperdirect trans-subthalamic pathway and through the direct and indirect trans-striatal pathways. The cannabinoid CB...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.14613
更新日期:2019-04-01 00:00:00
abstract::Lipocortin (annexin) 1 is a putative mediator of the inflammatory effects of glucocorticoids. By flow cytometric analysis (FACS) we have studied the effect of dexamethasone on the cellular localization of lipocortin 1. U-937 cells were incubated with or without 10 nM phorbol 12-myristate 13-acetate (PMA) to induce cel...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1994.tb13075.x
更新日期:1994-06-01 00:00:00
abstract::1. The present work describes the effects of inhibitors (amiloride and ethylisopropylamiloride) and activators (quinoxaline and phenylephrine) of the Na(+)-H+ exchanger on the outflow of dopamine in rat kidney slices loaded with L-dihydroxyphenylalanine (L-DOPA). 2. Incubation of kidney slices loaded with 50 microM L-...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1993.tb13608.x
更新日期:1993-06-01 00:00:00
abstract::1. We have investigated an aspect of the regulation of cortical pyramidal neurone activity. Microdialysis was used to assess whether topical application of drugs (in 10 microliter) to fill a burr hole over the frontal cortex, where part of the corticostriatal pathway originates, would change concentrations of the exci...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb15020.x
更新日期:1995-08-01 00:00:00
abstract::1. Three novel phenylglycine analogues; (RS)-alpha-methyl-3-chloro-4-phosphonophenylglycine (UBP1110), (RS)-alpha-methyl-3-methoxy-4-phosphonophenylglycine (UBP1111) and (RS)-alpha-methyl-3-methyl-4-phosphonophenylglycine (UBP1112) antagonised the depression of the fast component of the dorsal root-evoked ventral root...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705377
更新日期:2003-08-01 00:00:00
abstract::1. Piperazinylindoles (DPI 201-106, BDF 8784), drugs known to act on voltage-dependent Na(+)-channels, bind with very high affinity to a Ca2(+)-channel-associated phenylalkylamine receptor in Drosophila melanogaster head membranes. These compounds and (+)-tetrandrine, a naturally occurring Ca2(+)-antagonist, were the ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1991.tb12193.x
更新日期:1991-02-01 00:00:00
abstract::1. By use of a number of analogues of adenine nucleotides, the structure-activity relationships of the human platelet receptor for adenosine 5'-diphosphate (ADP) mediating increases in intracellular calcium were investigated, and compared with the known structure-activity relationships for induction by ADP of platelet...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1993.tb12869.x
更新日期:1993-03-01 00:00:00
abstract::1 Neuropeptide Y (NPY), peptide YY (PYY) and pancreatic polypeptide (PP) differentially activate three Y receptors (Y(1), Y(2) and Y(4)) in mouse and human isolated colon. 2 The aim of this study was to characterise Y(2) receptor-mediated responses in colon mucosa and longitudinal smooth muscle preparations from wild ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705298
更新日期:2003-06-01 00:00:00
abstract:BACKGROUND AND PURPOSE:The present study investigated whether the pathophysiological changes induced by burn and smoke inhalation are modulated by parenteral administration of Na(2)S, a H(2)S donor. EXPERIMENTAL APPROACH:The study used a total of 16 chronically instrumented, adult female sheep. Na(2)S was administered...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2009.00411.x
更新日期:2009-11-01 00:00:00
abstract::1. This study was designed to assess the molecular and cellular events involved in the up-regulation (and receptor supersensitivity) of brain alpha(2)-adrenoceptors as a result of chronic depletion of noradrenaline (and other monoamines) by reserpine. 2. Chronic reserpine (0.25 mg kg(-1) s.c., every 48 h for 6 - 14 da...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703963
更新日期:2001-04-01 00:00:00
abstract::1. The effects of an intrathecally administered benzodiazepine receptor (BZR) agonist (midazolam, up to 50 micrograms), antagonist (flumazenil, Ro 15-1788, 5 micrograms) and inverse agonist (Ro 19-4603, 15 micrograms) on nociception and on morphine-induced antinociception were studied in rats. 2. By themselves, none o...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1988.tb11486.x
更新日期:1988-04-01 00:00:00
abstract::1. Membrane effects of cromakalim (Crom; 50-300 microM) were examined in CA1 neurones recorded mainly by intracellular, single-electrode voltage-clamping in slices (from Sprague-Dawley rats) kept in an interface chamber at 33 degrees C. 2. In 14 cells held at -63 +/- 3.5 mV, in the presence of tetrodotoxin, kynurenic ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1994.tb17004.x
更新日期:1994-10-01 00:00:00
abstract:BACKGROUND AND PURPOSE:There is major evidence for the strong bi-directional interrelation of parenchymal cell apoptosis and leukocyte accumulation and inflammation in acute liver injury. Therefore, the aim of this in vivo study was to investigate the anti-apoptotic and anti-inflammatory potential of antileukoproteinas...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0707230
更新日期:2007-06-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Stress is believed to be associated with the development of neuropsychiatric disorders, including Alzheimer's disease (AD). We have studied mechanisms implicated in vulnerability to stress and the relationship with changes in AD-related markers. EXPERIMENTAL APPROACH:Anhedonia induced by a chron...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2011.01602.x
更新日期:2012-02-01 00:00:00
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, delivere...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb13372.x
更新日期:1995-04-01 00:00:00
abstract::1 Hypolipidaemic agents may increase biliary cholesterol in man, inducing a supersaturated bile. 2 To evaluate this possible side-effect, we have studied bile lipid secretion over a period of 8 h with intact enterohepatic circulation and 4 h with complete interruption in rats treated for two months with a salt of chol...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1981.tb10471.x
更新日期:1981-11-01 00:00:00
abstract:BACKGROUND AND PURPOSE:The effects of systemic treatment with indomethacin-loaded nanocapsules (IndOH-NC) were compared with those of free indomethacin (IndOH) in rat models of acute and chronic oedema. EXPERIMENTAL APPROACH:The following models of inflammation were employed: carrageenan-induced acute oedema (measured...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2009.00244.x
更新日期:2009-10-01 00:00:00
abstract::Previous studies have provided evidence for the presence on B cell membrane of adenosine receptors (P1-purinoceptors) of the A1-subtype which inhibit insulin secretion. In this work we have investigated the implication of a guanosine triphosphate (GTP) binding protein (G protein) in the A1 purinoceptor-induced inhibit...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1989.tb11775.x
更新日期:1989-01-01 00:00:00
abstract::1. We investigated the cytoprotective effect of low-dose nitric oxide (NO) on NO-induced cell death in mouse macrophage-like cell line RAW264. 2. Sodium nitroprusside (SNP), an NO donor, at a high concentration (4 mM) released cytochrome c from mitochondria and induced death in RAW264 cells. Acetyl-L-aspartyl-L-glutam...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705206
更新日期:2003-05-01 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
abstract::Despite the importance of members of the GPCR superfamily as targets of a broad range of effective medicines many GPCRs remain poorly characterised. GPR84 is an example. Expression of GPR84 is strongly up regulated in immune cells in a range of pro-inflammatory settings and clinical trials to treat idiopathic pulmonar...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bph.15248
更新日期:2020-09-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Kinins are pro-inflammatory peptides that are released during tissue injury, including that caused by inflammatory bowel disease. Herein, we assessed the role and underlying mechanisms through which the absence of kinin B(1) receptors exacerbates the development of dextran sulfate sodium (DSS)-i...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2012.02136.x
更新日期:2013-01-01 00:00:00
abstract::1 The reversible fatty acid amide hydrolase (FAAH) inhibitor OL135 reverses mechanical allodynia in the spinal nerve ligation (SNL) and mild thermal injury (MTI) models in the rat. The purpose of this study was to investigate the role of the cannabinoid and opioid systems in mediating this analgesic effect. 2 Elevated...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0706699
更新日期:2006-05-01 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 Mechanical and electrical responses to stimulation of the parasympathetic and sympathetic nerves were compared in the trachea isolated from normal guinea-pigs and from guinea-pigs sensitized to albumin and exposed repeatedly to inhaled albumin (a model of bronchial asthma). 2 Sensitized trachealis exhibited mechanic...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1987.tb11385.x
更新日期:1987-12-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Haem oxygenase-1 (HO-1) is induced by thiazolidinediones including rosiglitazone and exerts anti-inflammatory effects in various models. However, the molecular mechanisms underlying rosiglitazone-induced HO-1 expression remain largely unknown in human pulmonary alveolar epithelial cells (HPAEpiCs...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.14465
更新日期:2018-10-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Montelukast and S-carbocysteine have been used in asthmatic patients as an anti-inflammatory or mucolytic agent respectively. S-carbocysteine also exhibits anti-inflammatory properties. EXPERIMENTAL APPROACH:Ovalbumin (OVA) sensitized BALB/c mice were challenged with OVA for 3 days followed by s...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2010.00797.x
更新日期:2010-07-01 00:00:00
abstract::1. The variation with clock-hour in the behaviour of naive rats in a Y-maze has been recorded.2. The number of entries recorded was highest during the light period while the number of faecal boluses was highest during the dark period. Rearing showed a biphasic periodicity.3. The responses to LSD, mescaline and ampheta...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1973.tb08274.x
更新日期:1973-09-01 00:00:00
abstract::An attractive alternative to the use of direct agonists at the cannabinoid receptor type 1 (CB1) in the control of neuropathic pain may be to potentiate the actions of endogenous cannabinoids. Thus, the effects of AM404, an inhibitor of anandamide uptake, were assessed in an experimental model of neuropathic pain in r...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0706798
更新日期:2006-08-01 00:00:00
abstract::1 Atrial pacing at progressively increasing frequencies was performed on unanaesthetized dogs through electrodes placed aseptically in the wall of the right atrium and exteriorized in the neck region. 2 Heart rate and two atrioventricular conduction (AVC) parameters, namely the Wenckebach Point (one or two systole blo...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1982.tb09300.x
更新日期:1982-10-01 00:00:00