Abstract：
:1. We investigated the role of two conserved basic residues in the second transmembrane helix arginine 172 (R172) and lysine 179 (K179) of the VPAC(2) receptor. 2. Vasoactive intestinal polypeptide (VIP) activated VPAC(2) receptors with an EC(50) value of 7 nM, as compared to 150, 190 and 4000 nM at R172L, R172Q and K179Q-VPAC(2) receptors, respectively. It was inactive at K179I mutated VPAC(2) receptors. These results suggested that both basic residues were probably implicated in receptor recognition and activation. 3. The VPAC(2)-selective VIP analogue, [hexanoyl-His(1)]-VIP (C(6)-VIP), had a higher affinity and efficacy as compared to VIP at the mutated receptors. 4. VIP, Asn(3)-VIP and Gln(3)-VIP activated adenylate cyclase through R172Q receptors with EC(50) values of 190, 2 and 2 nM, respectively, and through R172L receptors with EC(50) values of 150, 12 and 8 nM, respectively. Asn(3)-VIP and Gln(3)-VIP behaved as partial agonists at the wild type receptor, with E(max) values (in per cent of VIP) of 75 and 52%, respectively. In contrast, they were more efficient than VIP (E(max) values of 150 and 150% at the R172Q VPAC(2) receptors, and of 400 and 360% at the R172L receptors, respectively). These results suggested that the receptor's R172 and the ligand's aspartate 3 are brought in close proximity in the active ligand-receptor complex. 5. The K179I and K179Q mutated receptors had a lower affinity than the wild-type receptors for all the agonists tested in this work: we were unable to identify the VIP amino acid(s) that interact with K179.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Vertongen P,Solano RM,Perret J,Langer I,Robberecht P,Waelbroeck Mdoi
10.1038/sj.bjp.0704195subject
Has Abstractpub_date
2001-08-01 00:00:00pages
1249-54issue
8eissn
0007-1188issn
1476-5381journal_volume
133pub_type
杂志文章abstract：:1. We studied the effect of bradykinin on plasma exudation in the airways of the anaesthetized guinea-pig in vivo. Tissue content of extravasated Evans blue dye was used as an index of protein exudation in the larynx, trachea, main bronchi and intrapulmonary airways (i.p.a.). 2. Bradykinin increased the content of Eva...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1990.tb14150.x
更新日期：1990-11-01 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：:The effects of carboxy-PTIO and hydroxocobalamin were studied on nitrergic transmission in anococcygeus and retractor penis muscles taken during post mortem examination from young male pigs. In both muscles under resting conditions, electrical field stimulation (EFS) caused contractions that were sensitive to tetrodot...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702496
更新日期：1999-05-01 00:00:00
abstract：:The NADPH oxidase (NOX) family of enzymes produces ROS as their sole function and is becoming recognized as key modulators of signal transduction pathways with a physiological role under acute stress and a pathological role after excessive activation under chronic stress. The seven isoforms differ in their regulation,...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.13532
更新日期：2017-06-01 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.tb07720.x
更新日期：1977-04-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Lung cancer is one of the leading causes of cancer death worldwide. Despite advances in therapy, conventional therapy is still the main treatment and has a high risk of chemotherapy resistance. Caspase-8 is involved in cell death and is a recognized marker for poor patient prognosis. EXPERIMENTA...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.13176
更新日期：2015-08-01 00:00:00
abstract：:The modulatory effects of protein kinase C (PKC) on the activation of cytosolic phospholipase A2 (cPLA2) and adenylyl cyclase (AC) have recently been described. Since the signalling cascades associated with these events play critical roles in various functions of macrophages, we set out to investigate the crosstalk be...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702219
更新日期：1998-12-01 00:00:00
abstract：:The cardiovascular effects of doxazosin, a quinazoline derivative related to prasozin were investigated and compared to prazosin in the rabbit. Radioligand binding studies using rabbit cerebral membranes showed that both doxazosin and prazosin were roughly equipotent at displacing [3H]-prazosin from specific binding s...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1985.tb09437.x
更新日期：1985-09-01 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:In addition to typical GPCR kinase (GRK)-/β-arrestin-dependent internalization, dopamine D3 receptor employed an additional GRK-independent sequestration pathway. In this study, we investigated the molecular mechanism of this novel sequestration pathway. EXPERIMENTAL APPROACH:Radioligand binding...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.12357
更新日期：2013-11-01 00:00:00
abstract：:1 The effects of the putative 5-hydroxytryptamine (5-HT) receptor antagonists, methysergide, mianserin and methergoline, the dopamine receptor antagonists, haloperidol, thioridazine and clozapine, and the noradrenaline (NA) receptor antagonists, phentolamine, phenoxybenzamine and propranolol on the behavioural respons...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1982.tb09278.x
更新日期：1982-09-01 00:00:00
abstract：:The effect of bath-applied luteinizing hormone-releasing factor (LHRF) was recorded in voltage-clamped bullfrog lumbar sympathetic neurones. At a holding potential of -- 30 mV, LHRF induced a steady inward (depolarizing) current and reduced membrane conductance; at -- 60 mV LHRF produced negligible inward current and ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1980.tb14547.x
更新日期：1980-03-01 00:00:00
abstract：:1. Fluoxetine (Prozac) is widely used as an antidepressant drug and is assumed to be a selective 5-hydroxytryptamine (5-HT) reuptake inhibitor (SSRI). Claims that its beneficial psychotropic effects extend beyond those in treatment of depression have drawn clinical and popular attention to this compound, raising the q...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701545
更新日期：1997-12-01 00:00:00
abstract：:1. Recently we and others have demonstrated a stereoselective inhibition of slowly activating human I(Ks) (KCNQ1/MinK) and homomeric KCNQ1 potassium channels by the enantiomers of the chromanol 293B. Here, we further characterized the mechanism of the 293B block and studied the influence of the 293B enantiomers on the...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0704421
更新日期：2001-12-01 00:00:00
abstract：:The detrimental actions of leptin on cardiovascular function are well established. Smith et al. report the novel finding of a reduction of infarct size by exogenous leptin when given at reperfusion. The involvement of the reperfusion injury salvage kinase (RISK) pathway in such reduction of infarct size and its relati...
journal_title：British journal of pharmacology
pub_type： 评论,杂志文章
doi：10.1038/sj.bjp.0706833
更新日期：2006-09-01 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：BACKGROUND AND PURPOSE:Here, we have compared the neurochemical profile of three new cathinones, butylone, mephedrone and methylone, in terms of their potential to inhibit plasmalemmal and vesicular monoamine transporters. Their interaction with 5-HT and dopamine receptors and their psychostimulant effect was also stud...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2012.01998.x
更新日期：2012-09-01 00:00:00
abstract：:In ring preparations of the rabbit external jugular vein contracted with the thromboxane-mimetic U-46619, submicromolar concentrations of 5-hydroxytryptamine (5-HT) and chemically related analogues produced relaxations that were dependent on the integrity of the vascular endothelium. The receptor mediating endothelium...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1987.tb10287.x
更新日期：1987-06-01 00:00:00
abstract：:Phytoestrogens are plant-derived dietary compounds with structural similarity to 17-β-oestradiol (E2), the primary female sex hormone. This structural similarity to E2 enables phytoestrogens to cause (anti)oestrogenic effects by binding to the oestrogen receptors. The aim of the present review is to present a state-of...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.13622
更新日期：2017-06-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Rosiglitazone is an anti-diabetic drug improving insulin sensitivity and glucose uptake in skeletal muscle and adipose tissues. However, several recent clinical trials suggest that rosiglitazone can increase the risk of cardiovascular ischaemia, although other studies failed to show such risks. T...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2011.01539.x
更新日期：2011-12-01 00:00:00
abstract：:1. Mild stress plus mild pain (solvent injection) applied daily to neonatal mice induces hormonal, behavioural and metabolic changes perduring in the adult life. 2. We investigated whether daily mild stress to neonatal mice induces also long-term defined changes of immune response, and whether immune changes are preve...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0704577
更新日期：2002-03-01 00:00:00
abstract：:1. Propranolol, a beta-adrenoceptor blocking drug with local anaesthetic and a direct myocardial depressant action, and MJ 1999, a beta-adrenoceptor blocking drug which has no local anaesthetic or intrinsic sympathomimetic action, were compared for beta-adrenoceptor blocking activity in man.2. Propranolol was 2.67 tim...
journal_title：British journal of pharmacology
pub_type： 临床试验,杂志文章
doi：10.1111/j.1476-5381.1970.tb10596.x
更新日期：1970-05-01 00:00:00
abstract：:Melatonin deprival in young rats induces alterations in cerebral arteriolar wall similar to those observed during aging: atrophy and a decrease in distensibility. In this study, we examined the effects of melatonin treatment on cerebral arteriolar structure and distensibility and on the lower limit of cerebral blood f...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0705629
更新日期：2004-02-01 00:00:00
abstract：BACKGROUND AND PURPOSE:PPAR-γ has been reported to be a protective regulator in ischaemia/reperfusion (I/R) injury. The receptor for advanced glycation end-products (RAGE) plays a major role in the innate immune response, and its expression is associated with PPAR-γ activation. Several angiotensin receptor blockers pos...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.12229
更新日期：2013-07-01 00:00:00
abstract：:1 About 45% of singly-housed male mice showed timidity (alert postures, running away, defensive postures) instead of aggression on interactions in pairs with group-housed male mice, though their partners did not show any aggression. The isolation-induced timidity was stable in repeated interactions. Timid mice also sh...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1975.tb07622.x
更新日期：1975-09-01 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 effects of gamma-aminobutyric acid (GABA) and related substances were examined in guinea-pig ileum longitudinal muscle.2 GABA at doses ranging from 10(-7) M to 3 x 10(-6) M elicited a relaxation while at higher doses (3 x 10(-6) M - 10(-4) M), as previously described, it caused a contraction followed by relaxati...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1983.tb08807.x
更新日期：1983-03-01 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：:1. beta-Bungarotoxin and other snake toxins with phospholipase activity augment acetylcholine release evoked from mouse motor nerve terminals before they produce blockade. This action of the toxins is independent of their phospholipase A2 activity, but the underlying mechanism for the facilitation of release is unclea...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1988.tb11595.x
更新日期：1988-07-01 00:00:00
abstract：:1. The regional binding of [3H]-(+)-5-methyl-10,11-dihydro-5H-dibenzo (a,d)cyclohepten-5,10-imine maleate ([3H]-(+)-MK 801) to sections of rat brain was measured by an in vitro quantitative autoradiographic technique. A heterogeneous distribution of binding sites was observed. 2. High values of binding were detected i...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1993.tb12845.x
更新日期：1993-03-01 00:00:00
