Abstract：
:1. The modulation of L-type calcium channel current (ICa) by fendiline, a diphenylalkylamine type of calcium channel blocker was investigated on guinea-pig ventricular myocytes by use of the whole-cell patch-clamp technique. 2. Fendiline-induced block of ICa is accompanied by modulation of the channel kinetics in a complex manner. The time course of ICa inactivation is significantly faster and the channel availability (f infinity) curve is shifted considerably to more negative potentials by fendiline. These findings can be interpreted qualitatively in terms of a modulated receptor. 3. When the 1,4-dihydropyridine agonist (4R, 4S)-Bay K 8644 was added in presence of 30 microM fendiline a further reduction of ICa instead of the expected stimulatory effect was observed. 4. A similar 'paradoxical' inhibition of ICa was produced by the pure agonist enantiomer (4S)-Bay K 8644. Thus this novel effect of Bay K 8644 cannot be attributed to changes in affinity of the 1,4-dihydropyridine receptor site for (4R)-Bay K 8644 during fendiline action. 5. The IC50 for fendiline was reduced to 3.0 +/- 0.1 microM (control value: 17.0 +/- 2.4 microM) and the Hill slope in its presence was increased to 1.90 +/- 0.1 (control value: 1.39 +/- 0.23) by 1 microM (4R, 4S)-Bay K 8644. 6. (4R,4S)-Bay K 8644 caused the expected stimulation of ICa in the presence of verapamil, diltiazem and nifedipine, overcoming the inhibitory effect of these calcium channel blockers. 7. The 'paradoxical' inhibitory effect of the agonist Bay K 8644 can be explained in terms of an allosteric interaction between fendiline and the dihydropyridine agonist.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Schreibmayer W,Tripathi O,Tritthart HAdoi
10.1111/j.1476-5381.1992.tb14308.xsubject
Has Abstractpub_date
1992-05-01 00:00:00pages
151-6issue
1eissn
0007-1188issn
1476-5381journal_volume
106pub_type
杂志文章abstract：:1. Transepithelial transport of a fluorescent derivative of octreotide (NBD-octreotide) was studied in freshly isolated, functionally intact renal proximal tubules from killifish (Fundulus heteroclitus). 2. Drug accumulation in the tubular lumen was visualized by means of confocal microscopy and was measured by image ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0703003
更新日期：2000-01-01 00:00:00
abstract：BACKGROUND AND PURPOSE:It is well known that adenine-based purines exert multiple effects on pain transmission. However, less attention has been given to the potential effects of guanine-based purines on pain transmission. The aim of this study was to investigate the effects of intraperitoneal (i.p.) and oral (p.o.) ad...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2009.00597.x
更新日期：2010-03-01 00:00:00
abstract：:1. A method is presented which enables the dissociation constant (KI) of a competitive, pseudo-irreversible or non-competitive antagonist-receptor complex to be estimated without knowledge of agonist concentrations. 2. The technique has been tested using sets of concentration-response data which simulated these variou...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1994.tb14047.x
更新日期：1994-01-01 00:00:00
abstract：:1. The cyclic nucleotide phosphodiesterase (PDE) of guinea-pig eosinophils was partially characterized and the effects of selective inhibitors of PDE isoenzymes upon opsonized zymosan (OZ)-stimulated respiratory burst were studied. 2. PDE activity in eosinophil lysates appeared to be membrane-associated, displayed sub...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1991.tb09790.x
更新日期：1991-06-01 00:00:00
abstract：:The incubation of rat peritoneal macrophages in the presence of staurosporine, a non-specific protein kinase inhibitor, induced interleukin-6 (IL-6) production in a time- and concentration-dependent manner at 6.3-63 nM, but at 210 nM, the stimulant effect on IL-6 production was reduced. The levels of IL-6 mRNA as dete...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702659
更新日期：1999-07-01 00:00:00
abstract：:1. The aims of the present study were to determine whether long-term 5-hydroxytryptamine (5-HT) reuptake blockade and inhibition of type-A monoamine oxidase (MAO-A) lead to an enhancement of the electrically evoked release of tritum from guinea-pig brain slices preloaded with [3H]-5-HT, and to assess the sensitivity o...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1994.tb17015.x
更新日期：1994-10-01 00:00:00
abstract：:1. To obtain direct evidence of abnormal eicosanoid biosynthesis in rats injected with anti-glomerular-basement-membrane antibodies (a-GBM), products derived from thromboxane A2 (TXA2) and prostacyclin (PGI2) were measured in 24 h urine collections before and after a-GBM. 2. Administration of a-GBM (9.5 mg) caused alb...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1991.tb09844.x
更新日期：1991-07-01 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：:1. The accumulation of (3)H-gamma-aminobutyric acid (GABA) by the isolated rat retina has been measured.2. When retinae were incubated at 37 degrees C in a medium containing (3)H-GABA, tissue:medium ratios of about 25:1 were attained after a 30 min incubation.3. After incubations of 40 min at 37 degrees C, almost all ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1973.tb08184.x
更新日期：1973-03-01 00:00:00
abstract：:1. The effect of bradykinin on the Na+-K+ pump of airway smooth muscle was investigated by measuring ouabain-sensitive (86)Rb(+) uptake in cultured guinea-pig tracheal smooth muscle cells. 2. Bradykinin induced a concentration-dependent increase in ouabain-sensitive (86)Rb(+) uptake, with an EC(50) of 3 nM (pD(2) = 8....
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0704198
更新日期：2001-08-01 00:00:00
abstract：:1. The effects of the non-selective endothelin (ET) receptor (ETA/ETB) antagonist, bosentan, on sciatic nerve dysfunction in experimental diabetes were investigated. 2. Rats with 5-6 weeks untreated streptozotocin-diabetes exhibited characteristic slowed motor nerve conduction velocity (mean +/- s.d., 36.6 +/- 3.4 m s...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1995.tb15888.x
更新日期：1995-05-01 00:00:00
abstract：:1. In decerebrated, non-spinalized rabbits, intrathecal administration of either of the selective 5-HT1A-receptor antagonists (S)WAY-100135 or WAY-100635 resulted in dose-dependent enhancement of the reflex responses of gastrocnemius motoneurones evoked by electrical stimulation of all myelinated afferents of the sura...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1996.tb16019.x
更新日期：1996-11-01 00:00:00
abstract：:1 The isolated perfused ear of the rabbit connected to the body only by its nerve, was used to investigate the influence of prostaglandin F2alpha on the algesic effect of bradykinin and acetylcholine. 2 Bradykinin and acetylcholine, following intra-arterial injection into the isolated perfused ear elicited a dose-rela...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1977.tb08390.x
更新日期：1977-03-01 00:00:00
abstract：:1. The action of the non-steroidal anti-inflammatory drugs (NSAID), sodium salicylate, aspirin, phenylbutazone and indomethacin was investigated on the migration of human polymorphonuclear cells (PMNs) and lymphocytes, using the system of migration of leucocytes from glass capillary tubes. 2. All NSAID produced a dose...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：
更新日期：1978-11-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Positive allosteric modulation of α4β2 nicotinic acetylcholine (nACh) receptors could add a new dimension to the pharmacology and therapeutic approach to these receptors. The novel modulator NS9283 was therefore tested extensively. EXPERIMENTAL APPROACH:Effects of NS9283 were evaluated in vitro ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2012.01989.x
更新日期：2012-09-01 00:00:00
abstract：:1. This study analyses the neural pathway involved in the modulation of gastric motor function by stress. 2. Systemic administration of low doses of endotoxin (40 microg kg(-1), i.v.) prevents the increase in gastric tone induced by 2-deoxy-D-glucose (200 mg kg(-1), i.v., 2-DG) in urethane-anaesthetized rats. 3. Funct...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0704258
更新日期：2001-09-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Central anti-nociceptive actions of baclofen involve activation of K+ channels. Here we assessed what types of K+ channel might participate in the peripheral anti-nociception induced by baclofen. EXPERIMENTAL APPROACH:Nociceptive thresholds to mechanical stimulation in rat paws treated with intr...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0706898
更新日期：2006-11-01 00:00:00
abstract：:1. Exogenous adenosine triphosphate (ATP) stimulated the short circuit current (SCC) in primary monolayer cultures of rat epididymal cells when added to the apical but not to the basolateral side of the monolayers. Half-maximal stimulation was achieved at 5 x 10(-8) M ATP. 2. The increase in SCC induced by ATP was dep...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1988.tb11770.x
更新日期：1988-12-01 00:00:00
abstract：:1. Previous patch clamp studies of oesophageal circular muscle cells showed that nitric oxide (NO) modulated the opening of Ca2(+)-activated K+ channels involved in mediating the inhibitory junction potentials (i.j.ps). This study clarified the role of Ca2+ release from the superficial sarcoplasmic reticulum (SR) in t...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1996.tb15661.x
更新日期：1996-08-01 00:00:00
abstract：:1. Chronic treatment with a combined ETA/ETB endothelin receptor antagonist has been shown to reduce blood pressure in experimental rat models of hypertension in which endothelin-1 gene overexpression occurs in the walls of blood vessels, particularly small, resistance-sized arteries, but not in those genetic or exper...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701224
更新日期：1997-07-01 00:00:00
abstract：:1 The responses of the smooth muscle of the capsule and blood vessels of the isolated, blood-perfused spleen of the dog to angiotensin, oxytocin and vasopressin have been investigated and compared to the actions of the catecholamines, adrenaline and noradrenaline.2 Increasing doses of each of the three polypeptides ca...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1975.tb06930.x
更新日期：1975-06-01 00:00:00
abstract：:Synaptic transmission in the isolated olfactory cortex slice from the rat was monitored by recording the surface field potentials evoked on lateral olfactory tract (LOT) stimulation. Catechol (approximately 0.05 to 2 mM) caused a concentration-dependent, partially reversible increase in the amplitudes of all field pot...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1986.tb10221.x
更新日期：1986-06-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Patients commonly take complementary medicines in conjunction with warfarin yet evidence supporting the safety or the risk of a herb-drug interaction is lacking. The aim of this study was to investigate the possible impact of two commonly used herbal medicines, garlic and cranberry, on the pharma...
journal_title：British journal of pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1038/bjp.2008.210
更新日期：2008-08-01 00:00:00
abstract：UNLABELLED:Increasing evidence suggests that an overactive endocannabinoid system (ECS) may contribute to the development of diabetes by promoting energy intake and storage, impairing both glucose and lipid metabolism, by exerting pro-apoptotic effects in pancreatic beta cells and by facilitating inflammation in pancre...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.13226
更新日期：2016-04-01 00:00:00
abstract：:1. Alterations of 5-hydroxytryptaminergic mechanisms are thought to play a special role in the pathogenesis of depression and antidepressant treatments are assumed to restore these changes. 2. We have used one of the most reliable models of depression, the olfactory bulbectomized rat to study the long term consequence...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701530
更新日期：1997-12-01 00:00:00
abstract：:1. The psychoactive cannabinoids (-)-delta 9-tetrahydrocannabinol ((-)-delta 9-THC) and the 1,1-dimethyl-heptyl homologue of (-)-11-hydroxy-delta 8-tetrahydrocannabinol ((-)-DMH) both inhibited electrically-evoked contractions of the mouse isolated vas deferens and the myenteric plexus-longitudinal muscle preparation ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1992.tb09088.x
更新日期：1992-04-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Obesity is a risk factor for several inflammation-based diseases including arthritis. We investigated the anti-nociceptive and anti-inflammatory effects of the cannabinoid CB1 receptor antagonist rimonabant in lean and diet-induced obese female rats with arthritis induced by complete Freund's adj...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0707138
更新日期：2007-03-01 00:00:00
abstract：BACKGROUND AND PURPOSE:5-HT (serotonin) regulates various physiological functions, both directly and via enteric neurons. The present study investigated the role of endogenous 5-HT and 5-HT3 receptors in the pathogenic mechanisms involved in colonic inflammation, especially in relation to substance P (SP) and the neuro...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.13482
更新日期：2016-06-01 00:00:00
abstract：:1 A rat isolated gastric mucosal preparation was used to monitor histamine output and acid secretion during stimulation by different secretagogues. 2 In non-stimulated preparations, spontaneous histamine output decreased over 450 min. 3 Stimulation of secretion with 4 (5)-methylhistamine or dibutyryl cyclic adenosine ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1982.tb09190.x
更新日期：1982-05-01 00:00:00
abstract：:Ginsenoside Rg1, an active ingredient in ginseng, was previously shown to be a novel class of potent phytoestrogen. The present study aims at investigating the molecular mechanisms involved in mediating its actions in human breast cancer (MCF-7) cells. Rg1 (1 pM) stimulates cell proliferation (P<0.01) and estrogen-res...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0706640
更新日期：2006-03-01 00:00:00
