Abstract：
:1. Mouse islets were used to define the characteristics and study the mechanisms of the stimulation of insulin release by compound AZ-DF 265, 4-[[N-(alpha-phenyl-2-piperidino-benzyl) carbamoyl]methyl] benzoic acid, a substituted benzoic acid with an asymmetric carbon atom. 2. At a non-stimulatory concentration of glucose (3 mM), (-)-AZ-DF 265 reversibly inhibited 86Rb efflux from islet cells, depolarized the beta-cell membrane, induced electrical activity, stimulated 45Ca efflux, and triggered insulin release. Maximum inhibition of 86Rb efflux occurred at 0.03 microM (-)-AZ-DF 265, whereas the threshold concentration for stimulation of release was 0.1 microM. Omission of extracellular Ca2+ abolished all effects of the drug but the inhibition of 86Rb efflux. 3. At a stimulatory concentration of glucose (10 mM), (-)-AZ-DF 265 reversibly increased 86Rb efflux, potentiated electrical activity, augmented 45Ca efflux, and increased insulin release. Maximum stimulation of 86Rb efflux and insulin release was obtained with 0.03 microM (-)-AZ-DF 265. Omission of extracellular Ca2+ abolished all effects of the drug. 4. The potency of (-)-AZ-DF 265 was similar to that of glibenclamide, whereas the (+)-enantiomer was about 10 times less potent on 86Rb efflux and insulin release. 5. It is concluded that, like sulphonylureas, compound AZ-DF 265 decreases K+ permeability of the beta-cell membrane and thereby causes depolarization. This activates voltage-dependent Ca channels, permits Ca2+ influx and eventually stimulates insulin release. Its stereoselectivity may help to elucidate the mechanisms of K channel blockade and, hence, lead to the design of more potent and specific insulinotropic drugs.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Garrino MG,Henquin JCdoi
10.1111/j.1476-5381.1988.tb11405.xsubject
Has Abstractpub_date
1988-01-01 00:00:00pages
61-8issue
1eissn
0007-1188issn
1476-5381journal_volume
93pub_type
杂志文章abstract：:The properties of the ATPase released during electrical field stimulation (EFS) (8 Hz, 25 s) of the sympathetic nerves of the superfused rabbit isolated vas deferens were investigated. Superfusate collected during EFS rapidly metabolised exogenous ATP (100 microM) and 50% was broken down in 5.67+/-0.65 min. The main m...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0703662
更新日期：2000-11-01 00:00:00
abstract：:1. We compared the relaxant effect of pituitary adenylate cyclase activating peptide (PACAP) 1-27 with that of a newly developed PACAP 1-27 analogue, [Arg15,20,21Leu17]-PACAP-Gly-Lys-Arg-NH2, in the guinea-pig trachea and primate bronchi in vitro (n = 4-5). 2. In the guinea-pig trachea precontracted by a submaximally ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701310
更新日期：1997-08-01 00:00:00
abstract：:The severity of anaemic decerebrate rigidity was quantitatively determined by measuring the frequency of electromyographic potentials in the rat. Some oxazolidinones markedly reduced the severity of this decerebrate rigidity in a dose-dependent manner, (4S,5R)-4-(2-methylpropyl)-3- [3-(perhydroazepin-1-yl)propyl]-5-ph...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1986.tb11138.x
更新日期：1986-09-01 00:00:00
abstract：:1. The antithrombotic action of argatroban, a synthetic thrombin inhibitor, was studied in a canine model of coronary cyclic flow having some of the characteristics of acute unstable angina. Heparin was studied as a reference anticoagulant. 2. Localized endothelial damage was induced in the circumflex coronary artery ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1996.tb15460.x
更新日期：1996-06-01 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. The ionic dependence of [(3)H]-metaraminol transport by rabbit ventricular slices was studied.2. Transport was Na(+) dependent. Choline, Li(+), K(+), Rb(+) or Cs(+) could not be substituted for Na(+).3. Transport was K(+) dependent. Rb(+) and Cs(+), but not Li, could be substituted for K(+), their relative potencie...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1971.tb09936.x
更新日期：1971-01-01 00:00:00
abstract：:Tannins are a heterogeneous group of high MW, water-soluble, polyphenolic compounds, naturally present in cereals, leguminous seeds and, predominantly, in many fruits and vegetables, where they provide protection against a wide range of biotic and abiotic stressors. Tannins exert several pharmacological effects, inclu...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.13630
更新日期：2017-06-01 00:00:00
abstract：:The influence of endogenous and exogenous acidic amino acids on the binding of [3H]-MK-801, a selective, non-competitive antagonist of N-methyl-D-aspartate (NMDA) receptors, has been investigated in rat cerebral cortex crude synaptic membranes (CSM). Removal of endogenous glutamate and aspartate from CSM by repeated w...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1987.tb10295.x
更新日期：1987-06-01 00:00:00
abstract：:The effects of the angiotensin-converting-enzyme inhibitor (ACEI) ramiprilat, the angiotensin II type 1 receptor antagonist (AT(1)A) candesartan, and the combination of both drugs on infarct size (IS) resulting from regional myocardial ischaemia were studied in pigs. Both ACEI and AT(1)A reduce myocardial IS by a brad...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0703544
更新日期：2000-09-01 00:00:00
abstract：:Oxidized low density lipoproteins (oxLDL) are thought to play a major role in atherosclerosis. OxLDL act in part through alteration of intracellular signalling pathways in cells of the vascular wall. We recently reported that the EGF receptor (EGFR) signalling pathway is activated by lipid peroxidation products (among...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0703981
更新日期：2001-04-01 00:00:00
abstract：:1. Previous work from our laboratory has shown that cannabis induces aggressive behaviour in rats that have been deprived of rapid eye movement (REM) sleep. It was suggested that this effect was related to brain catecholamines, with dopamine playing an agonist role and noradrenaline an inhibitory one. The present pape...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1977.tb08429.x
更新日期：1977-11-01 00:00:00
abstract：:The interaction of a new nonribose ligand (LUF5831) with the human adenosine A1 receptor was investigated in the present study. Radioligand binding experiments were performed in the absence and presence of diverse allosteric modulators on both wild-type (wt) and mutant (T277A) adenosine A1 receptors. Thermodynamic dat...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0706655
更新日期：2006-03-01 00:00:00
abstract：:Substance P and substance K (neurokinin A) (dose range: 0.08-80 nmol kg-1) were tested for their effects on gastrointestinal propulsion in the rat. The peptides were given by intraperitoneal injection concurrently with the intragastric administration of a test meal containing charcoal and 51Cr. Examination 3 min after...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1985.tb09462.x
更新日期：1985-09-01 00:00:00
abstract：:1. Previous studies had shown that adenosine and adenine nucleotides including adenosine 5'-triphosphate (ATP) caused contraction of the rat colon muscularis mucosae via P1 and P2Y-purinoceptors respectively, and that the stable ATP analogue adenylyl 5'-(beta,gama- methylene)diphosphonate (AMPPCP) had an unexpected di...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1992.tb14265.x
更新日期：1992-02-01 00:00:00
abstract：:The phenanthrene-derivative 9-phenanthrol is a recently identified inhibitor of the transient receptor potential melastatin (TRPM) 4 channel, a Ca(2+) -activated non-selective cation channel whose mechanism of action remains to be determined. Subsequent studies performed on other ion channels confirm the specificity o...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.12582
更新日期：2014-04-01 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：:1 The effect of 5-hydroxytryptamine (5-HT) on acid secretion by a rat isolated stomach preparation has been studied. 2 5-HT at 10(-5)M in the serosal bathing fluid produced significant inhibition of the acid secretory responses to histamine, pentagastrin and isoprenaline but was without effect on basal secretion or th...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1983.tb09371.x
更新日期：1983-01-01 00:00:00
abstract：:1. The effect of trimebutine on the voltage-dependent inward Ca2+ current was investigated by the whole-cell voltage-clamp technique in single smooth muscle cells from rabbit ileum. 2. Trimebutine (3-100 microM) reduced the Ca2+ current in a concentration-dependent manner. The inhibitory effect on the Ca2+ current was...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1993.tb13823.x
更新日期：1993-09-01 00:00:00
abstract：:Forty-eight isolated rat hearts were perfused with Krebs solution and with [(3)H]-(-)-noradrenaline ([(3)H]-NA) containing 4.5 nCi/ml in 50 ng/ml, as described by Iversen (1963). To groups of six, cocaine was added to [(3)H]-NA in concentrations of 400 nM, 2 and 10 muM. To the rest Tween 80, 25 mug/ml was added to [(3...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1974.tb10686.x
更新日期：1974-07-01 00:00:00
abstract：:Inhalation of cyclopropane in dogs, by the closed circuit method, for a fixed period, produced an emetic response during recovery from anaesthesia. Bilateral surgical ablation of the emetic chemoreceptor trigger zone of the area postrema rendered the dogs refractory to several times (3-6) the threshold emetic dose of ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1971.tb07174.x
更新日期：1971-09-01 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：:Antibiotics are an essential part of modern medicine. The emergence of antibiotic-resistant mutants among bacteria is seemingly inevitable, and results, within a few decades, in decreased efficacy and withdrawal of the antibiotic from widespread usage. The traditional answer to this problem has been to introduce new a...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1038/sj.bjp.0707432
更新日期：2007-12-01 00:00:00
abstract：BACKGROUND AND PURPOSE:The renal sodium-glucose cotransporter 2 (SGLT2) plays an important role in the reuptake of filtered glucose in the proximal tubule and therefore may be an attractive target for the treatment of diabetes mellitus. This study characterizes the pharmacological profile of TS-071 ((1S)-1,5-anhydro-1-...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2011.01340.x
更新日期：2011-09-01 00:00:00
abstract：:1. The effect of ondansetron, a selective 5-hydroxytryptamine3 (5-HT3) receptor antagonist, was studied in morphine-addicted rats. Morphine-dependence and tolerance, induced by drinking increasing concentrations of morphine sulphate in 5% sucrose solution for 3 weeks, were demonstrated by the naloxone-precipitated wit...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1996.tb15504.x
更新日期：1996-06-01 00:00:00
abstract：:1. Experiments were designed to determine whether endothelium-dependent relaxing factor(s) released by acetylcholine from the canine femoral artery influences the membrane potential of coronary arterial smooth muscle. 2. The membrane potential was recorded in small canine coronary arteries (internal diameter less than...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1988.tb10306.x
更新日期：1988-03-01 00:00:00
abstract：:3,4-Methylenedioxymethamphetamine (MDMA, 'ecstasy') administration to rats produces hyperthermia if they are housed in normal or warm ambient room temperature (Ta) conditions (>or=20 degrees C), but hypothermia when in cool conditions (Ta journal_title：British journal of pharmacology pub_type： 杂志文章 doi：10.1038/sj.bjp.0706318 更新日期：2005-09-01 00:00:00
abstract：:1. The action of substance P (SP) on the release of gamma-aminobutyric acid (GABA) and acetylcholine (ACh) and on contraction were studied in strips of the guinea-pig urinary bladder. Substance P induced a dose-dependent contraction of strips of guinea-pig urinary bladder (EC50 = 1.2 x 10(-9) M). This contraction was ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1989.tb12615.x
更新日期：1989-10-01 00:00:00
abstract：:1. The interactions between two K+ channel openers, cromakalim and SR 44866 (infused i.v. at equihypotensive doses), and the sympathetic nervous system at the systemic and regional (mesentery, kidney, hindlimb) vascular levels were investigated in the pithed spontaneously hypertensive rat (SHR) by use of the pulsed Do...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1990.tb15846.x
更新日期：1990-07-01 00:00:00
abstract：:1. The binding of 2-[125I]-iodomelatonin to chicken brain membranes, and the inhibition of binding by melatonin, N-acetyltryptamine and luzindole, were examined at temperatures between 4 degrees C and 37 degrees C. 2. At all temperatures studied, the binding affinity (Kd or Ki) for 2-[125I]-iodomelatonin, melatonin (b...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1994.tb14059.x
更新日期：1994-01-01 00:00:00
abstract：:1. Effects of morphine sulphate (1.25, 2.5, 5, 10, 20 and 40 mg/kg i.p.) on locomotor activity of male rats were observed for 8 h after single doses in non-tolerant rats. The lower three doses had only an excitatory effect, whereas the higher three doses caused initial depression followed by a delayed excitatory effec...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1972.tb06866.x
更新日期：1972-10-01 00:00:00
