Abstract:
:1. [35S]t-butylbicyclophosphorothionate (TBPS) is a high affinity ligand for the picrotoxin site of GABA(A) receptors. Here we examined TBPS binding to the cloned receptors made of alpha 1, alpha 3 or alpha 6 in combination with beta 2 or beta 2 and gamma 2 subunits, in the presence of GABA and several allosteric ligands (diazepam, methyl 6,7-dimethoxy-4-methyl-beta-carboline-3-carboxylate (DMCM), 3 alpha,21-dihydroxy-5 alpha-pregnan-20-one (5 alpha-THDOC), pentobarbitone and Zn). The cloned receptors were transiently expressed in SF-9 insect cells by infecting with recombinant baculoviruses. 2. In alpha beta subtypes, GABA at nanomolar concentrations enhanced TBPS binding but inhibited binding at micromolar concentrations. Half maximal GABA concentrations for enhancement or inhibition of TBPS binding were correlated with high and low affinity GABA binding sites, respectively, in individual subtypes. The maximal enhancement of binding also varied according to the alpha isoform (alpha 3 beta 2 > alpha 1 beta 2). In alpha beta gamma subtypes, TBPS binding was unaffected by GABA at nanomolar concentrations, but was inhibited by GABA at micromolar concentrations. Addition of gamma 2 thus appeared to abolish conformational coupling between high affinity GABA sites and TBPS sites, and also altered low affinity GABA sites; in particular, the half maximal GABA concentration for inhibition of TBPS binding changed from > 100 (alpha 6 beta 2) to 1 microM (alpha 6 beta 2 gamma 2). 3. Allosteric ligands also altered TBPS binding to sensitive GABA(A) receptor subtypes. For instance,diazepam only in the alpha 1 beta2 gamma 2 and alpha 3 beta 2 gamma 2 subtypes, and 5 alpha-THDOC in all the subtypes enhanced TBPS binding in the absence of GABA, and intensified the inhibitory effect of GABA. Pentobarbitone exhibited only the latter effect in all the subtypes we examined.4. DMCM and Zn, inhibitors of GABA-induced Cl currents in alpha beta gamma and alpha beta subtypes, respectively,produced opposite effects to agonists, decreasing TBPS binding in the absence of GABA and attenuating(or eliminating in the case of Zn) the inhibitory effect of GABA on TBPS binding.5. These results show that GABA binding sites and their conformational coupling with TBPS sites are differentially affected by the alpha isoform (particularly alpha 6 as compared to alpha l or alpha 3) and by quaternary interactions involving the gamma 2 subunit. Moreover, changes in TBPS binding by allosteric ligands include not only direct (allosteric) effects on TBPS sites but also indirect effects via GABA sites, and are consistent with their known subtype selectivity and functionality from previous studies.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Im WB,Pregenzer JF,Thomsen DRdoi
10.1111/j.1476-5381.1994.tb13185.xsubject
Has Abstractpub_date
1994-08-01 00:00:00pages
1025-30issue
4eissn
0007-1188issn
1476-5381journal_volume
112pub_type
杂志文章abstract::1. The noradrenaline concentration in the lung was less than 0.5 mug/g in eight animal species.2. In the cat, dog, rabbit and goat, tyramine produced a fall in pulmonary resistance, which was reduced by the administration of either reserpine or cocaine. Although an infusion of noradrenaline increased the content of th...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1970.tb08525.x
更新日期:1970-02-01 00:00:00
abstract::The gastrointestinal (GI) tract is exposed to a large array of proteases, under both physiological and pathophysiological conditions. The discovery of G protein-coupled receptors activated by proteases, the protease-activated receptors (PARs), has highlighted new signaling functions for proteases in the GI tract, part...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1038/sj.bjp.0705750
更新日期:2004-04-01 00:00:00
abstract::1. We have compared the effects of ouabain on the maintenance of gap junctional communication in rat aortic A7r5 smooth muscle cells, monkey COS-1 fibroblasts and human HeLa epithelial cells. 2. Ouabain (1 mM) interrupted dye coupling between confluent A7r5 cells within approximately 1 h, and high concentrations of ou...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705556
更新日期:2003-12-01 00:00:00
abstract::1. Hamster stomach strips in vitro are useful test preparations for the assay of prostaglandins E and F in the nanogram concentration range. Three-minute cycles can be used for long periods without spontaneous contractions or significant base-line instability.2. The mean percentage error and the precision index of six...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1973.tb08542.x
更新日期:1973-12-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Avoiding danger and finding food are closely related behaviours that are essential for surviving in a natural environment. Growing evidence supports an important role of gut-brain peptides in modulating energy homeostasis and emotional-affective behaviour. For instance, postprandial release of pa...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.13456
更新日期:2016-06-01 00:00:00
abstract::A number of cholinoceptor antagonists used in the treatment of Parkinson's disease were examined for their ability to antagonize either the muscarinic receptor-mediated inhibition of dopamine D1 receptor-stimulated adenylyl cyclase or the muscarinic receptor-mediated stimulation of [3H]-inositol phosphates ([3H]-IPs) ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb15474.x
更新日期:1996-06-01 00:00:00
abstract::1. We studied the effects of flash photolysis on the novel enantiomeric cardiac inotropes EMD 57033 (a calcium sensitizer) and EMD 57439 (a phosphodiesterase III inhibitor) in rat isolated ventricular trabeculae. 2. In skinned trabeculae, EMD 57439 had no effect on force production, consistent with lack of an active c...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb15641.x
更新日期:1996-08-01 00:00:00
abstract::1. The effect of basal tension (transmural tensions 235 +/- 29 mg wt (low tension: equivalent to approximately 16 mmHg) and 305 +/- 34 mg wt (high tension: equivalent to 35 mmHg)) on rat pulmonary resistance artery responses to endothelin-1 (ET-1) and the selective ET(B)-receptor agonist sarafotoxin S6c (S6c) were stu...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701682
更新日期:1998-03-01 00:00:00
abstract::LDL cholesterol (LDL-C) plays a central role in the progression of atherosclerosis. Statin therapy for lowering LDL-C reduces the risk of atherosclerotic cardiovascular disease and is the recommended first-line treatment for patients with high LDL-C levels. However, some patients are unable to achieve an adequate redu...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bph.14851
更新日期:2019-08-29 00:00:00
abstract::Psoriasis is a chronic inflammatory disease affecting 1-3% of the general population. Among psoriatic patients, 5-40% are affected by psoriatic arthritis. Due to the chronic nature of the disease, patients suffer from substantial psychological and financial burdens, thus adding to a significantly impaired quality of l...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1476-5381.2010.00702.x
更新日期:2010-06-01 00:00:00
abstract::Peroxisome proliferator activated receptors (PPAR)s are nuclear transcription factors of the steroid receptor super-family. One member, PPARgamma, a critical transcription factor in adipogenesis, is expressed in ECV304 cells, and when activated participates in the induction of cell death by apoptosis. Here we describe...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703628
更新日期:2000-10-01 00:00:00
abstract::1. Inhibition of human polymorphonuclear leucocyte (PMN) function by adenosine was studied with respect to effects of adenosine on intracellular cyclic AMP and calcium during the PMN respiratory burst. 2. The adenosine analogue 5'-N-ethylcarboxamide-adenosine (NECA) and L-N6-phenyl-isopropyl-adenosine (L-PIA) inhibite...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1989.tb12028.x
更新日期:1989-07-01 00:00:00
abstract::1. To examine further the potentiation by endothelin-1 on the vascular response to sympathetic stimulation, we studied the isometric response of isolated segments, 2 mm long, from the rabbit central ear artery to electrical field stimulation (1-8 Hz), under different conditions, at 37 degrees C and during cooling (30 ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701324
更新日期:1997-08-01 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::Spontaneous inhibitory postsynaptic currents (i.p.s.cs) were recorded in voltage-clamped CA1 neurones in rat hippocampal slices. The exponential decay of i.p.s.cs was prolonged by concentrations of sodium pentobarbitone as low as 50 microM. With concentrations up to 100 microM, there was no change in the amplitude or ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1985.tb10563.x
更新日期:1985-07-01 00:00:00
abstract::1. The effects of intradermally injected prostaglandins (PGs) E(1), E(2), F(1alpha) and F(2alpha) have been examined in the rat and in man.2. PGE(1) and PGE(2) caused an increase in local vascular permeability in rat skin; their potency was comparable with that of other putative mediators of inflammation (histamine, b...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1971.tb09934.x
更新日期:1971-01-01 00:00:00
abstract::1 Dose-related increases in airways resistance (Raw) and decreases in dynamic lung compliance (Cdyn) were recorded in guinea-pigs and rats following intravenous injection of propranolol and of the cardioselective beta-adrenoceptor blocking drugs, atenolol and practolol. 2 The bronchoconstriction reached a peak in 2 to...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1979.tb10846.x
更新日期:1979-07-01 00:00:00
abstract:BACKGROUND AND PURPOSE:The glucagon-like peptides GLP-1 and GLP-2 are secreted from enteroendocrine L-cells following nutrient ingestion. Drugs that increase activity of the GLP-1 axis are highly successful therapies for type 2 diabetes, and boosting L-cell secretion is a potential strategy for future diabetes treatmen...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2011.01561.x
更新日期:2012-01-01 00:00:00
abstract::1. The vasodilator response to acetylcholine (ACh) was investigated in the aortic arches of the leopard frog (Rana pipiens). 2. With adrenaline pre-constricted preparations, both ACh and sodium nitroprusside (SNP) caused concentration-dependent relaxations. Damage to the endothelial layer abolished relaxations to ACh,...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb15568.x
更新日期:1996-07-01 00:00:00
abstract:BACKGROUND AND PURPOSE:While selective, bitter tasting, TAS2R agonists can relax agonist-contracted airway smooth muscle (ASM), their mechanism of action is unclear. However, ASM contraction is regulated by Ca²⁺ signalling and Ca²⁺ sensitivity. We have therefore investigated how the TAS2R10 agonists chloroquine, quinin...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.12460
更新日期:2014-02-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Heat-sensitive transient receptor potential vanilloid (TRPV) channels are expressed in various epithelial tissues regulating, among else, barrier functions. Their expression is well established in the distal nephron; however, we have no data about their presence in podocytes. As podocytes are ind...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.14052
更新日期:2017-12-01 00:00:00
abstract::1. The effects of intrathecally (i.t.) injected substance P (SP), neurokinin A (NKA), [beta-Ala8]NKA (4-10) and [MePhe7]neurokinin B (NKB) at T13 thoracic spinal cord level were investigated on renal excretion of water, sodium and potassium in the conscious saline-loaded rat. Antagonists selective for NK1 (RP 67580), ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701223
更新日期:1997-07-01 00:00:00
abstract::1 The effects of alpha- and beta-adrenoceptor stimulants on the histamine-forming capacity (HFC) of human isolated leucocytes have been studied, in vitro.2 It was confirmed that antigen significantly stimulates the HFC of human leucocytes.3 beta-Adrenoceptor stimulants, such as isoprenaline and salbutamol (10(-6)-10(-...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1974.tb09702.x
更新日期:1974-10-01 00:00:00
abstract::1. The effects of cocaine, 6-hydroxydopamine (6-OHDA), reserpine and 17-beta-oestradiol on the sensitivity of the rat anococcygeus muscle to noradrenaline (NA), acetylcholine (ACh) and KCl were investigated.2. Cocaine (10(-5)M) increased the sensitivity of the anococcygeus to NA (100-fold) but not to ACh or KCl.3. 6-O...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1973.tb17261.x
更新日期:1973-11-01 00:00:00
abstract::1. Adenosine 5'-triphosphate (ATP) is known to augment cardiac contractile activity and cause an increase in intracellular Ca(2+) concentration ([Ca(2+)](i)) in isolated cardiomyocytes. However, no information regarding the ATP-mediated signal transduction in the myocardium in congestive heart failure (CHF) is availab...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705867
更新日期:2005-01-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Endothelin-1 (ET-1) is increased in patients with sickle cell disease and may contribute to the development of sickle cell nephropathy. The current study was designed to determine whether ET-1 acting via the ETA receptor contributes to renal injury in a mouse model of sickle cell disease. EXPERI...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.13380
更新日期:2016-01-01 00:00:00
abstract::We have shown earlier that activation of metabotropic glutamate (mGlu) receptors using a group I-specific mGlu receptor agonist, (RS)-3,5-dihydroxyphenylglycine (DHPG), can induce long-term depression (LTD) in the CA1 region of the hippocampus. In an attempt to determine the signal transduction mechanisms involved in ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703905
更新日期:2001-03-01 00:00:00
abstract::The effect of trimetazidine (TMZ), an anti-anginal drug, on the mechanical response of the guinea-pig ductus arteriosus placed under conditions of mild hypoxia (PO2 approximately equal to 75 mmHg) was investigated. When the PO2 of the bathing solution was 75 mmHg, TMZ caused a dose-dependent increase in tension. The m...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1985.tb12936.x
更新日期:1985-02-01 00:00:00
abstract::1. The role of nitic oxide (NO) derived from L-arginine in the regional vasodilator effects of endothelin-1 has been investigated in anaesthetized, spontaneously hypertensive (SH) rats in which autonomic reflexes were abolished by ganglion blockade. The experimental design incorporated animals infused with phenylephri...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1992.tb09049.x
更新日期:1992-03-01 00:00:00
abstract::Carbon monoxide (CO) is firmly established as an important, physiological signalling molecule as well as a potent toxin. Through its ability to bind metal-containing proteins, it is known to interfere with a number of intracellular signalling pathways, and such actions can account for its physiological and pathologica...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bph.12760
更新日期:2015-03-01 00:00:00