Abstract：
:1. The sinus node inhibitors UL FS 49 and DK-AH 269 reduce heart rate by slowing diastolic depolarization rate in the sino-atrial (SA) node, which might originate from the use-dependent blockade of a hyperpolarization-activated current If. A hyperpolarization-activated current Ih, which is present in many types of neurons, is similar to If. We studied the effects of these drugs on Ih in cultured mouse dorsal root ganglion (DRG) neurons. 2. With the whole-cell patch-clamp technique use-dependent block of Ih was observed. The steady-state block following a voltage-clamp pulse train (1-s steps from -38 to -108 mV applied at 0.5 Hz) was dependent on drug concentration and showed an apparent Kd of 0.1 and 0.79 microM with DK AH 269 and UL-FS 49 respectively. 3. The rate of block increased linearly with drug concentration. The rate of recovery from block was, however, much slower compared to cardiac tissue. 4. There was no significant effect of UL-FS 49 on the activation curve. 5. At high concentrations of UL-FS 49 a clear association of the drug with the open channel was observed. 6. When the cell was stimulated at a frequency of 3 Hz, a distinct hyperpolarization was observed in the presence of extracellular Cs+ or when Ih was blocked with UL-FS 49, but not in the absence of Cs+ and UL-FS 49. 7. These results indicate that Ih protects the cell against hyperpolarizations and subsequent inexcitability. The action of the drugs on the hyperpolarization-activated current in cardiac and neuronal tissue show some similarities; however, some pronounced differences indicate that different subtypes of the channel might exist.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Raes A,Van de Vijver G,Goethals M,van Bogaert PPdoi
10.1038/sj.bjp.0702153subject
Has Abstractpub_date
1998-10-01 00:00:00pages
741-50issue
4eissn
0007-1188issn
1476-5381journal_volume
125pub_type
杂志文章abstract：BACKGROUND AND PURPOSE:Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors, and three subtypes (α, β and γ) have been identified. PPAR activation has been reported to decrease renal injury and markers of glomerular dysfunction in models of renal ischemia/reperfusion (I/R). How...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2010.01032.x
更新日期：2011-01-01 00:00:00
abstract：:1 The actions of ethylenediamine (EDA) and structurally related compounds were investigated by microiontophoresis in Wistar rats. 2 EDA inhibited, via a bicuculline-sensitive mechanism, the spontaneous firing rate of all cortical and pallidal cells tested. 3 The results with the analogues suggest that two amine groups...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1982.tb08761.x
更新日期：1982-01-01 00:00:00
abstract：:1 A study was made of desensitization in chronically denervated and in normally innervated mouse soleus muscles. 2 Very high concentrations of acetylcholine produced small contractions of the innervated muscles; these were reduced in size when the addition was repeated 1 min after wash-out. 3 Desensitization in innerv...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1975.tb07620.x
更新日期：1975-09-01 00:00:00
abstract：:Inotropic actions of the endogenous enkephalins, leucine enkephalin [( Leu] enkephalin) and methionine enkephalin [( Met] enkephalin), and derivatives, [D-Ala2-methionine] enkephalinamide (DAMEA) and [D Ala2-leucine]enkephalinamide (DALEA) were tested, alone or in combination with noradrenaline (NA), (+/-)-isoprenalin...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1985.tb08888.x
更新日期：1985-06-01 00:00:00
abstract：:1. The affinities of a number of alpha 1-adrenoceptor antagonists were determined by displacement of [3H]-prazosin binding from cloned human alpha 1A-adrenoceptors (previously designated cloned alpha 1c subtype), alpha 1B alpha 1D and rat alpha 1D-adrenoceptors, stably expressed in rat-1 fibroblasts. Functional affini...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1995.tb15907.x
更新日期：1995-07-01 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. Caffeine, 0.6-20.0 mM, altered the duration of the action potential recorded from kitten papillary muscles; low concentrations shortened and high concentrations prolonged the action potential.2. Caffeine, 20 mM, prolonged the action potential by delaying the final phase of repolarization.3. Caffeine, 2.0-20.0 mM in...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1973.tb08153.x
更新日期：1973-01-01 00:00:00
abstract：:We investigated the effects of cocaine and corticosterone on the noradrenaline-induced relaxation of rat oesophageal smooth muscle in the absence and presence of the selective beta2-antagonist, ICI 111,551. It was found that the concentration-response curve (CRC) of noradrenaline was not shifted by ICI 118,551 at 1 mi...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1995.tb16396.x
更新日期：1995-10-01 00:00:00
abstract：:Adrenomedullin (AM) has two known receptors formed by the calcitonin receptor-like receptor (CL) and receptor activity-modifying protein (RAMP) 2 or 3: we report the effects of the antagonist fragments of human AM and CGRP (AM22-52 and CGRP8-37) in inhibiting AM at human (h), rat (r) and mixed species CL/RAMP2 and CL/...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0705472
更新日期：2003-10-01 00:00:00
abstract：BACKGROUND AND PURPOSE:The age-related decline in vasorelaxation is largely due to ceramide-induced induction of phosphatase 2A (PP2A), which limits nitric oxide synthase (eNOS) phosphorylation at stimulatory sites. We hypothesized that ceramide accumulation was from an age-related loss of endothelial glutathione (GSH)...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/bjp.2008.28
更新日期：2008-04-01 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：:Mitochondrial permeability transition pore (mPTP) opening plays a critical role in cardiac reperfusion injury and its prevention is cardioprotective. Tumour cell mitochondria usually have high levels of hexokinase isoform 2 (HK2) bound to their outer mitochondrial membranes (OMM) and HK2 binding to heart mitochondria ...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.12899
更新日期：2015-04-01 00:00:00
abstract：:1. The effect of prolonged anti-hypertensive drug treatment on the blood pressure of conscious spontaneously hypertensive rats (SH-rats), and of age-matched normotensive Sprague-Dawley rats was determined during the development of hypertension in SH-rats and in the early stages of established hypertension. A compariso...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1975.tb07588.x
更新日期：1975-08-01 00:00:00
abstract：:1 Administration of isoprenaline by aerosol inhalation to man results in over 80% being metabolized to the sulphate conjugate.2 The majority of an inhaled dose is probably swallowed since the metabolic pattern resembles that after an oral dose.3 Isoprenaline, administered in aqueous solution directly into the bronchia...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1974.tb08593.x
更新日期：1974-04-01 00:00:00
abstract：:It was confirmed that morphine administration in vivo produced a selective decrease in the calcium content of synaptosomal fractions prepared from rat cerebral cortices. This effect was prevented by naloxone. 2 After morphine or naloxone, there were no changes in the sodium, potassium and magnesium contents of any of ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1976.tb10379.x
更新日期：1976-08-01 00:00:00
abstract：:1 The synthesis of several butyrophenone analogues of haloperidol is described. 2 The effects of these compounds on alpha-adrenoceptors were evaluated by examining their ability to reduce alpha 1-stimulated K+ release from rat parotid slices and to displace [3H]-phentolamine from human platelet membrane alpha 2-adreno...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1982.tb08775.x
更新日期：1982-01-01 00:00:00
abstract：:1. Intracellular recordings were made from neurones in vitro in the rat substantia nigra zona compacta and ventral tegmental area; the neurones had the characteristic properties of dopamine-containing cells, and fired action potentials spontaneously. 2. Cocaine (1-10 microM) inhibited spontaneous firing, hyperpolarize...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1990.tb12998.x
更新日期：1990-04-01 00:00:00
abstract：:(1) Stimulation of the vanilloid receptor-1 (TRPV1) results in the activation of nociceptive and neurogenic inflammatory responses. Poor specificity and potency of TRPV1 antagonists has, however, limited the clarification of the physiological role of TRPV1. (2) Recently, iodo-resiniferatoxin (I-RTX) has been reported ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0705110
更新日期：2003-03-01 00:00:00
abstract：:1. Arachidonic acid caused larger contractions to indomethacin-tested guinea-pig trachea than in control tracheae. 2. No change in contractions was obtained in tracheae treated with 5,8, 11, 14, eicosatetraynoic acid (ETYA 10 micro M). 3. ETYA (100 micro M) blocked the effect of indomethacin on arachidonic acid-induce...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1982.tb09250.x
更新日期：1982-08-01 00:00:00
abstract：:1. The effects of the glycine/NMDA receptor antagonist, (+)-HA-966 on the neurochemical and behavioural responses to amphetamine have been determined in the mouse and rat. 2. In vehicle-treated control mice, (+)-HA-966 (30-100 mg kg-1) did not affect dopamine synthesis in either the nucleus accumbens or striatum and w...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1991.tb12372.x
更新日期：1991-08-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Transforming growth factor beta1 (TGFbeta1) is generated in atherosclerotic and injured vessel walls. We examined whether the endothelial-to-mesenchymal transdifferentiation induced by TGFbeta1 affects endothelial functions. EXPERIMENTAL APPROACH:Bovine aortic endothelial cells (BAECs) were trea...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0706883
更新日期：2006-10-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Fibrosis, a pathological accumulation of collagen in tissues, represents a major global disease burden. Effective characterization of potential antifibrotic drugs has been constrained by poor formation of the extracellular matrix in vitro, due to tardy procollagen processing by collagen C-protein...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2009.00387.x
更新日期：2009-11-01 00:00:00
abstract：:There is evidence that cannabinoid-based medicines that are selective for different targets in the cannabinoid signalling system (e.g. receptors, inactivation mechanism, enzymes) might be beneficial in basal ganglia disorders, namely Parkinson's disease (PD) and Huntington's disease (HD). These benefits not only inclu...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/j.1476-5381.2008.00088.x
更新日期：2009-04-01 00:00:00
abstract：:It is well documented that metabolic syndrome (i.e. a group of risk factors, such as abdominal obesity, elevated blood pressure, elevated fasting plasma glucose, high serum triglycerides and low cholesterol level in high-density lipoprotein), which raises the risk for heart disease and diabetes, is associated with inc...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.12960
更新日期：2015-03-01 00:00:00
abstract：:1. Human big-endothelin-1 (big-ET-1) and endothelin-1 (ET-1) are equipotent as pressor agents and produce a significant change in mean arterial blood pressure (MAP) in anaesthetized guinea-pigs (2 nmol kg-1: peak delta MAP: 23 +/- 6 mmHg and 26 +/- 5 mmHg, respectively). 2. Unlike big-ET-1, big-endothelin-3 (big-ET-3)...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1991.tb12448.x
更新日期：1991-10-01 00:00:00
abstract：:1. The pharmacological characteristics of RP 67580, a non-peptide tachykinin NK1 receptor antagonist, and its effects on a reflex response evoked by stimulation of primary afferent fibres, were examined in isolated neonatal spinal cord preparations of the rat. Potentials were recorded extracellularly from a lumbar ven...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1994.tb17116.x
更新日期：1994-12-01 00:00:00
abstract：:1. The present study was designed to characterize the nociceptive response induced by protein kinase C (PKC) peripheral activation and to investigate if this biochemical event is important for the nociceptive response induced by formaldehyde, and bradykinin (BK). 2. Intraplantar injection of phorbol-12,13-didecanoate ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0704434
更新日期：2002-01-01 00:00:00
abstract：BACKGROUND AND PURPOSE:While the 5-HT and Rho-kinase (ROCK) pathways have been implicated in the development of pulmonary arterial hypertension (PAH), the nature of any interactions between them remain unclear. This study investigated a role for ROCK in 5-HT-regulated proliferative responses in lung fibroblasts in vivo...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/bjp.2008.310
更新日期：2008-10-01 00:00:00
abstract：BACKGROUND AND PURPOSE:The type-5 PDE inhibitor vardenafil reduces myocardial infarct size in situ, following ischemia/reperfusion, when applied at reperfusion in animal models. Little is known about the underlying protective signaling. Here, we test whether vardenafil is protective in rat isolated hearts and in a cell...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/bjp.2008.71
更新日期：2008-05-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Non-invasive in vivo imaging of cannabinoid CB2 receptors using PET is pursued to study neuroinflammation. The purpose of this study is to evaluate the in vivo binding specificity of [18 F]MA3, a CB2 receptor agonist, in a rat model with local overexpression of human (h) CB2 receptors. METHODS:[...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.14564
更新日期：2019-05-01 00:00:00
