Abstract：
BACKGROUND AND PURPOSE:Ajmaline is a widely used antiarrhythmic drug. Its action on voltage-gated ion channels in skeletal muscle is not well documented and we have here elucidated its effects on Na(+) and K(+) channels. EXPERIMENTAL APPROACH:Sodium (I(Na)) and potassium (I(K)) currents in amphibian skeletal muscle fibres were recorded using 'loose-patch' and two-microelectrode voltage clamp techniques (2-MVC). Action potentials were generated using current clamp. KEY RESULTS:Under 'loose patch' clamp conditions, the IC(50) for I(Na) was 23.2 microM with Hill-coefficient h=1.21. For I(K), IC(50) was 9.2 microM, h=0.87. Clinically relevant ajmaline concentrations (1-3 microM) reduced peak I(Na) by approximately 5% but outward I(K) values were reduced by approximately 20%. Na(+) channel steady-state activation and fast inactivation were concentration-dependently shifted towards hyperpolarized potentials ( approximately 10 mV at 25 microM). Inactivation curves were markedly flattened by ajmaline. Peak-I(K) under maintained depolarisation was reduced to approximately 30% of control values by 100 microM ajmaline. I(K) activation time constants were increased at least two-fold. Lower concentrations (10 or 25 microM) reduced steady-state-I(K) slightly but peak-I(K) significantly. Action potential generation threshold was increased by 10 microM ajmaline and repolarisation prolonged. CONCLUSIONS AND IMPLICATIONS:Ajmaline acts differentially on Na(+) and K(+) channels in skeletal muscle. This suggests at least multiple sites of action including the S4 subunit. Our data may provide a first insight into specific mechanisms of ajmaline-ion channel interaction in tissues other than cardiac muscle and could suggest possible side-effects that need to be further evaluated.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Friedrich O,V Wegner F,Wink M,Fink RHdoi
10.1038/sj.bjp.0707194subject
Has Abstractpub_date
2007-05-01 00:00:00pages
82-93issue
1eissn
0007-1188issn
1476-5381pii
0707194journal_volume
151pub_type
杂志文章abstract：:1. This study describes the effects of hypoxia on relaxing responses and cAMP production induced by the known vasodilator peptides: alphaCGRP, amylin (AMY) and adrenomedullin (AM) on isolated pig coronary arteries in vitro. 2. Hypoxic incubation increased the vasorelaxant effect of alphaCGRP (four-fold; P<0.05), AMY (...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0706232
更新日期：2005-07-01 00:00:00
abstract：:1. Effects of neuropeptides of the vasopressin family on Cl(-) secretion have not yet been reported in lung. Using the 16HBE14o- bronchial epithelial cell line, we investigated their action on Cl(-) secretion. 2. In symmetrical Cl(-) solutions, basolateral application of arginine vasotocin (AVT), oxytocin or isotocin ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0706103
更新日期：2005-04-01 00:00:00
abstract：:1 The responses of excitatory junctions on locust skeletal muscle fibres to iontophoretically applied L-glutamic acid and DL-ibotenic acid, a rigidly extended analogue of glutamate, were recorded by means of intracellular microelectrodes.2 Iontophoresis of L-glutamate to junctional sites produced transient depolarizat...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1979.tb13675.x
更新日期：1979-06-01 00:00:00
abstract：:We compared the modulation of synaptic transmission by adenosine A(1) receptors in the hippocampus of aged (24 months) and young adult rats (6 weeks). The adenosine A(1) receptor agonist, N(6)-cyclopentyladenosine, was less potent (P:<0.05) to inhibit synaptic transmission in aged (EC(50)=53 nM) than young adult (EC(5...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0703736
更新日期：2000-12-01 00:00:00
abstract：:1 Mechanical and electrical responses to stimulation of the parasympathetic and sympathetic nerves were compared in the trachea isolated from normal guinea-pigs and from guinea-pigs sensitized to albumin and exposed repeatedly to inhaled albumin (a model of bronchial asthma). 2 Sensitized trachealis exhibited mechanic...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1987.tb11385.x
更新日期：1987-12-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Protease-activated receptor 1 (PAR1) has been demonstrated to be involved in the pathogenesis of viral diseases. However, its role remains controversial. The goal of our study was to investigate the contribution of PAR1 to respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) infecti...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.14084
更新日期：2018-01-01 00:00:00
abstract：:1. Endothelial cell damage in glomeruli and kidney arterioles appears to play a pivotal role in glomerular inflammatory diseases. Glomerular endothelial cells, a specialized microvascular cell type involved in the regulation of glomerular ultrafiltration, die by apoptosis in response to tumour necrosis factor-alpha (T...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702726
更新日期：1999-08-01 00:00:00
abstract：:1. The effects of dimethothiazine have been studied on the response of afferent fibres from primary and secondary endings of muscle spindles in the soleus muscle of the decerebrate cat during stretching of the muscle under controlled conditions.2. Dimethothiazine in doses of 1 to 4 mg/kg intravenously reduced the disc...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1970.tb10360.x
更新日期：1970-07-01 00:00:00
abstract：:1. A grease-gap technique has been used to measure d.c. potentials, in response to the application of excitatory amino acids and electrical stimulation of the Schaffer collateral-commissural pathway, in the CA1 region of rat hippocampal slices. The actions of L-glutamate (L-Glu) have been quantified and compared to th...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1991.tb12178.x
更新日期：1991-02-01 00:00:00
abstract：:Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease where the additional presence of pulmonary hypertension (PH) reduces survival. In particular, the presence of coexistent pulmonary vascular disease in patients with advanced lung parenchymal disease results in worse outcomes than either diagnosis alone. This ...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.15036
更新日期：2021-01-01 00:00:00
abstract：:Noradrenaline (NA) and adrenaline (Ad) are modulators of cytokine production. Here we investigated the role of these neurotransmitters in the regulation of macrophage inflammatory protein (MIP)-1alpha expression. Pretreatment of RAW 264.7 macrophages with NA or Ad decreased, in a concentration-dependent manner (1 nM-1...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702179
更新日期：1998-11-01 00:00:00
abstract：:1 Plasma noradrenaline concentrations were similar in rats following unilateral renal arterial constriction (two kidney Goldblatt model) and in sham-operated control rats. 2 The development of hypertension was not affected by pretreatment with intracisternal injections of 6-hydroxydopamine. 3 These data suggest that s...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1977.tb08406.x
更新日期：1977-10-01 00:00:00
abstract：:1. The cyclic analogue of dopamine, 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (ADTN) was injected into the lateral ventricle or bilaterally into the nucleus accumbens or caudate nucleus of conscious rats and its effect on locomotor activity was investigated. 2. When given intraventricularly, ADTN produced so...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1975.tb07416.x
更新日期：1975-05-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Muscarinic toxins (MTs) are snake venom peptides named for their ability to interfere with ligand binding to muscarinic acetylcholine receptors (mAChRs). Recent data infer that these toxins may have other G-protein-coupled receptor targets than the mAChRs. The purpose of this study was to systema...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2011.01468.x
更新日期：2011-09-01 00:00:00
abstract：:Calcitonin gene-related peptide (CGRP) is believed to play a pivotal role in the pathogenesis of migraine via activation of CGRP receptors in the trigeminovascular system. The CGRP receptor antagonist, BIBN4096BS, has proven efficacy in the acute treatment of migraine attacks and represents a new therapeutic principle...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0705966
更新日期：2004-11-01 00:00:00
abstract：:In non-allergic subjects, histamine induced a reduction of minimal nasal cross-sectional area (Amin) and an increase in albumin release into nasal lavage. The effect of histamine on albumin release was inhibited by pretreatment with NG-nitro-L-arginine methyl ester (L-NAME), 1 mumol but not by D-NAME, 1 mumol. L-NAME,...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1995.tb16653.x
更新日期：1995-09-01 00:00:00
abstract：:The binding of [3H]-iloprost (ZK36374) to NCB-20 membranes revealed a single population of high affinity receptors (KD = 9.55 nM, Bmax = 431 fmol mg-1 protein) and a low affinity, non-saturable binding component. Desensitization of prostacyclin-responsiveness of NCB-20 cells is induced by culture in the presence of th...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1985.tb08852.x
更新日期：1985-05-01 00:00:00
abstract：:1. The action of adrenaline on the K(+) balance of the isolated heart was found to depend on the ionic composition and the temperature of the perfusion fluids used.2. When the perfusion fluid contained 145 mM Na(+), 1.7 mM Ca(++) and 3-9 mM K(+), adrenaline caused the hearts to gain K(+); when the K(+) concentration w...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1969.tb08012.x
更新日期：1969-07-01 00:00:00
abstract：:1 Picrotoxin selectively and reversibly suppressed the inhibitory action of gamma-aminobutyric acid (GABA), but not that of glycine, taurine or beta-alanine, on the frequency of spontaneous spike discharges in guinea-pig cerebellar slices. Strychnine reversibly suppressed the inhibitory action of glycine, taurine or b...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1976.tb07650.x
更新日期：1976-05-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Partial agonists selective for α4β2 nicotinic ACh receptors have been developed for smoking cessation as they induce weak activation of native α4β2* receptors and inhibit effect of nicotine. However, it is unclear whether at brain functions there is an existence of receptor reserve that allows we...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2011.01628.x
更新日期：2012-02-01 00:00:00
abstract：:1. The irreversible opioid receptor antagonist beta-chlornaltrexamine (beta-CNA) has been shown previously to have agonist activity in the guinea-pig ileum preparation. However, the receptor type or types mediating this effect have not been established. 2. In this study, the agonism of beta-CNA was investigated by use...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1988.tb16569.x
更新日期：1988-09-01 00:00:00
abstract：:1. The action of angiotensin on the circular and longitudinal muscle of the human colon has been studied in vitro. The ED50 value (g/ml) of circular muscle was 8.7 x 10(-8) and of longitudinal muscle 3.1 x 10(-8), while the corresponding figures for acetylcholine were 1.6 x 10(-6) and 1.1 x 10(-6), respectively. Angio...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1970.tb09553.x
更新日期：1970-05-01 00:00:00
abstract：:1. PD 81,723 has been shown to enhance binding of adenosine to A1 receptors by stabilizing G protein-receptor coupling ('allosteric enhancement'). Evidence has been provided that in the perfused hearts and isolated atria PD 81,723 causes a sensitization to adenosine via this mechanism. 2. We have studied the effect of...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701254
更新日期：1997-07-01 00:00:00
abstract：:A linear correlation between amplitude of miotic response and initial pupil diameter has been demonstrated in rabbits using various concentrations of pilocarpine HC1. The same correlation was found when published results in humans using carbachol were examined and it is likely that the correlation also applies to pilo...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1970.tb10635.x
更新日期：1970-11-01 00:00:00
abstract：:1. The effect of a single injection of the monoamine oxidase inhibitor, tranylcypromine, administered intravenously (20 mg/kg) or into the lateral cerebral ventricle (5-10 mg), on hypothalamic and rectal temperature, has been investigated.2. Intravenous tranylcypromine causes a significant rise in body temperature, wh...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1970.tb10594.x
更新日期：1970-05-01 00:00:00
abstract：:BACKGROUND AND PURPOSE The Ca(2+) paradox is an important phenomenon associated with Ca(2+) overload-mediated cellular injury in myocardium. The present study was undertaken to elucidate molecular and cellular mechanisms for the development of the Ca(2+) paradox. EXPERIMENTAL APPROACH Fluorescence imaging was performe...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2010.00986.x
更新日期：2010-12-01 00:00:00
abstract：:1. The possibility that tachykinin NK1 receptors are involved in the plasma extravasation evoked by intradermal (i.d.) injection of Phoneutria nigriventer venom (PNV) in rat dorsal skin in vivo has been investigated. 2. Local oedema formation induced by the i.d. injection of test agents was measured by the extravascul...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1996.tb15402.x
更新日期：1996-05-01 00:00:00
abstract：:Antihistamine induced cognitive decline was evaluated using positron emission tomography (PET) measurement of histamine H1 receptor (H1R) occupancy and regional cerebral blood flow (rCBF). Cognitive performance in attention-demanding task deteriorated dose-dependently and the effects were statistically significant aft...
journal_title：British journal of pharmacology
pub_type： 临床试验,杂志文章
doi：10.1038/sj.bjp.0702994
更新日期：2000-01-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Macropinocytosis is involved in many pathologies, including cardiovascular disorders, cancer, allergic diseases, viral and bacterial infections. Unfortunately, the currently available pharmacological inhibitors of macropinocytosis interrupt other endocytic processes and have non-specific endocyto...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.14429
更新日期：2018-09-01 00:00:00
abstract：:Burimamide, an H(2)-receptor blocking agent, has been shown capable of blocking the uptake and metabolism of [(14)C]-histamine, both in the guinea-pig isolated atrium and in murine neoplastic mast cells. This occurs even at concentrations far below the dose range capable of blocking the positive chronotropic effect of...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1973.tb08384.x
更新日期：1973-10-01 00:00:00
