Abstract：
BACKGROUND AND PURPOSE:Sulphatides are sulphated glycosphingolipids expressed on the surface of many cell types, particularly neurones. Changes in sulphatide species or content have been associated with epilepsy and Alzheimer's disease. As the large conductance, calcium sensitive K(+) channel (BK(Ca)) are modulated by membrane lipids, the aim of the study was to explore possible effects of sulphatides on BK(Ca) channels. EXPERIMENTAL APPROACH:Using patch-clamp techniques, we studied effects of exogenous sulphatides on BK(Ca) channels expressed in Chinese hamster ovary cells. KEY RESULTS:Sulphatides reversibly increased the whole-cell current and the single channel open probability of BK(Ca) channels dose-dependently. The EC(50) value on the channel at +10 mV was 1.6 microM and the Hill coefficient was 2.5. In inside-out patches, sulphatides increased the single channel open probability from both intra- and extra-cellular faces of the membrane, but more effectively with external application. Furthermore, activation of the channels by sulphatides was independent of intracellular Ca(2+) concentration. Sulphatides also shifted the activation curve of the channels to less positive membrane potentials. Mutant BK(Ca) channels lacking a 59 aminoacid region important for amphipath activation (STREX) were less activated by the sulphatides. CONCLUSIONS AND IMPLICATIONS:Sulphatides are novel activators of BK(Ca) channels, independent of intracellular Ca(2+) or other signalling molecules but partly dependent on the STREX sequence of the channel protein. As changes of sulphatide content are associated with neuronal dysfunction, as in epilepsy and Alzheimer's disease, our results imply that these effects of sulphatides may play important pathophysiological roles in regulation of BK(Ca) channels.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Chi S,Qi Zdoi
10.1038/sj.bjp.0706947subject
Has Abstractpub_date
2006-12-01 00:00:00pages
1031-8issue
8eissn
0007-1188issn
1476-5381pii
0706947journal_volume
149pub_type
杂志文章abstract：:BACKGROUND AND PURPOSE Selective hyperpolarization activated, cyclic nucleotide-gated channel (HCN) blockers represent an important therapeutic goal due to the wide distribution and multiple functions of these proteins, representing the molecular correlate of f- and h-current (I(f) or I(h) ). Recently, new compounds ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2011.01782.x
更新日期：2012-05-01 00:00:00
abstract：:1 Prostaglandin and thromboxane release from the term pregnant (Day 22) rat uterus in vitro has been measured by radioimmunoassay and gas chromatography combined with mass spectrometry. 2 Prostacyclin (prostaglandin I2, PGI2) and thromboxane A2 (TXA2) (measured as their metabolites, 6-oxo-PGF1 alpha and TXB2, respecti...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1981.tb16773.x
更新日期：1981-05-01 00:00:00
abstract：:1 Human luteal tissue slices from days 18, 21 and 25 of the menstrual cycle were superfused in vitro with Medium 199 alone or containing cloprostenol (1 microgram/ml). Concentrations of progesterone, oestradiol-17beta and prostaglandins F2alpha and E2 were determined in the superfusate samples. 2 Secretion of steroids...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1977.tb07518.x
更新日期：1977-07-01 00:00:00
abstract：:1. We have taken advantage of our recent development of highly potent and specific phosphinic inhibitors of endopeptidase 3.4.24.15 to examine the putative contribution of the enzyme in the secretion of A beta by HK293 transfected cells overexpressing the wild type and the Swedish (Sw) double mutated form of beta APP7...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701151
更新日期：1997-06-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Transient receptor potential melastatin 3 (TRPM3) proteins form non-selective but calcium-permeable membrane channels, rapidly activated by extracellular application of the steroid pregnenolone sulphate and the dihydropyridine nifedipine. Our aim was to characterize the steroid binding site by an...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.12521
更新日期：2014-02-01 00:00:00
abstract：:The effect of acute, streptozotocin-induced diabetes on the affinity (KD), density (Bmax) and selectivity of specific, high affinity binding sites for [125I]-endothelin [( 125I]-ET) in rat cardiac membrane fragments was determined. Three days after a single i.v. bolus dose of streptozotocin (60 mg kg-1), the density o...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1989.tb12552.x
更新日期：1989-08-01 00:00:00
abstract：:1. In guinea-pigs previously sensitized with ovalbumin, the intra-plantar administration of the antigen induced dose-dependent and sustained oedema. An intense infiltrate of neutrophils and eosinophils was observed at the peak of the oedema (4 h). 2. Oedema induced by ovalbumin at the doses of 50 or 200 micrograms/paw...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1994.tb13038.x
更新日期：1994-05-01 00:00:00
abstract：:1. In the presence of indomethacin (IM, 10 microM) and N omega-nitro-L- arginine (L-NOARG, 0.3 mM), acetylcholine (ACh) induces an endothelium-dependent smooth muscle hyperpolarization and relaxation in the rat isolated hepatic artery. The potassium (K) channel inhibitors, tetrabutylammonium (TBA, 1 mM) and to a lesse...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1996.tb15327.x
更新日期：1996-04-01 00:00:00
abstract：:1. The efflux and influx of tryptophan across the synaptosomal plasma membrane has been studied under a variety of experimental conditions, in order to examine the mechanism by which depolarization enhances the efflux of tryptophan from superfused synaptosomes. 2. Efflux of [3H]-tryptophan from preloaded superfused sy...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1988.tb11440.x
更新日期：1988-02-01 00:00:00
abstract：:1. The rat spinal cord in vitro has been used to assess the effect of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) on the dorsal root evoked extracellular ventral root reflex (DR-VRR) and the intracellular excitatory postsynaptic potential (e.p.s.p.) in ventral horn neurones and motoneurones. 2. CNQX (1-5 microM) produ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1992.tb12754.x
更新日期：1992-10-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Lysophosphatidylinositol (LPI), a lipid signalling molecule, activates GPR55 and elevates intracellular Ca(2+). Here, we examine the actions of LPI in the rat resistance mesenteric artery and Ca(2+) responses in endothelial cells isolated from the artery. EXPERIMENTAL APPROACH:Vascular responses...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.13107
更新日期：2015-06-01 00:00:00
abstract：:The contractile responses of the rabbit isolated coeliac and mesenteric arteries to five agonists (angiotensin, adrenaline, histamine, acetylcholine and 5-hydroxytryptamine), but not to K+, were potentiated by indomethacin (8.4 microM) The potentiation was similar whether indomethacin was added 1 h before or during th...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1983.tb10714.x
更新日期：1983-11-01 00:00:00
abstract：:This study was performed to characterize the receptor subtypes involved in the endothelin stimulation of phospholipase D (PLD) in rat cortical astrocytes in primary culture. PLD activity was determined by measuring the formation of [32P]phosphatidylbutanol in [32P]orthophosphate prelabelled cells stimulated in the pre...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701997
更新日期：1998-08-01 00:00:00
abstract：:1. The macroscopic currents induced in cultured rat melanotrophs by exogenous gamma-aminobutyric acid (GABA) were analysed using the patch clamp recording technique. 2. Using various concentrations of intra- and extracellular chloride it was demonstrated that the conductance activated by GABA was chloride selective. S...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1987.tb11359.x
更新日期：1987-11-01 00:00:00
abstract：:1. The effects of forskolin, prostaglandin E1 (PGE1), dibutyryl cyclic AMP (db cyclic AMP), dibutyryl cyclic GMP (db cyclic GMP) and 3-isobutyl-l-methyl-xanthine (IBMX) were investigated on the expression of tissue factor and thrombomodulin activities on the surface of human saphenous vein endothelial cells (HSVEC) in...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1993.tb13526.x
更新日期：1993-05-01 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：:1. The anti-inflammatory effect of alpha-trinositol (D-myo-inositol-1,2,6-trisphosphate) on oedema formation, microvascular protein leakage and interstitial fluid pressure (Pif) in rat skin after frostbite injury, was investigated. Alpha-trinositol (40 mg kg body weight(-1)) was administered intravenously as a bolus b...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702442
更新日期：1999-03-01 00:00:00
abstract：:1. This study was undertaken to investigate whether, after a brief exposure of guinea-pig isolated ileum and rabbit jejunum to bremazocine, a kappa-opioid agonist also possessing antagonist activity at mu-opioid receptors, the addition of opioid antagonists produced withdrawal contractures. Our aim was to verify in th...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1995.tb13334.x
更新日期：1995-03-01 00:00:00
abstract：:1. The nature and cellular mechanisms that are responsible for endothelium-dependent relaxations resistant to indomethacin and NG-nitro-L-arginine methyl ester (L-NAME) were investigated in phenylephrine (PE) precontracted isolated carotid arteries from the rabbit. 2. In the presence of the cyclo-oxygenase inhibitor, ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0700945
更新日期：1997-02-01 00:00:00
abstract：:1. In order to determine whether activation of adenosine triphosphate (ATP)-sensitive K+ channels exclusively explains the hypoxia- and ischaemia-induced action potential shortening, effects of tolbutamide and glibenclamide on changes in action potential duration (APD) during hypoxia, metabolic blockade or experimenta...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1991.tb12294.x
更新日期：1991-05-01 00:00:00
abstract：:Amyotrophic lateral sclerosis (ALS) is an adult onset disorder characterized by progressive neuromuscular junction (NMJ) dismantling and degeneration of motor neurons leading to atrophy and paralysis of voluntary muscles responsible for motion and breathing. Except for a minority of patients harbouring genetic mutatio...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.15276
更新日期：2020-09-28 00:00:00
abstract：:The Concise Guide to PHARMACOLOGY 2013/14 provides concise overviews of the key properties of over 2000 human drug targets with their pharmacology, plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand propert...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.12448
更新日期：2013-12-01 00:00:00
abstract：BACKGROUND AND PURPOSE:The aim of this study was to determine whether the apelin/APJ system is altered in human cardiovascular disease by investigating whether the expression of apelin or its receptor is altered at the protein level. EXPERIMENTAL APPROACH:Radioligand binding studies were used to determine apelin recep...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2010.00821.x
更新日期：2010-08-01 00:00:00
abstract：:1 The fate of (15S)-15-methyl prostaglandin E(2) methyl ester and 16,16-dimethyl prostaglandin E(2) in the pulmonary circulation of rat isolated lungs was compared with that of prostaglandin E(2) by means of bioassay.2 Calculated on the basis of height of response of the assay tissues, the inactivation of prostaglandi...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1978.tb08456.x
更新日期：1978-02-01 00:00:00
abstract：:1. The subtypes of endothelin receptors that mediate the effects of endothelin-1 (ET-1) on mean arterial pressure (MAP), heart rate (HR), mean circulatory filling pressure (MCFP), arterial resistance (RA), cardiac output (CO) and venous resistance (RV) were characterized in 9 groups of pentobarbitone-anaesthetized rat...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701474
更新日期：1997-11-01 00:00:00
abstract：:1. Effects of an orally active non-peptide (BK) B2 receptor antagonist, FR173657 ((E)-3-(6-acetamido-3-pyridyl)-N-[N-[2,4-dichloro-3-[(2-methyl-8-quinoli nyl) oxymethyl]phenyl]-N-methylaminocarbonylmethyl] acrylamide) on the plasma exudation in rat carrageenin-induced pleurisy were investigated. 2. Plasma exudation in...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701194
更新日期：1997-06-01 00:00:00
abstract：:1 PD 117302, a new nonpeptide opioid compound shown in in vitro studies to be a selective kappa-opioid agonist, has been evaluated in vivo for antinociceptive activity and other effects characteristic of kappa-receptor activation. 2 Dose-related long lasting antinociception was produced by PD 117302 against a mechanic...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1987.tb11398.x
更新日期：1987-12-01 00:00:00
abstract：:The novel urotensin-II (U-II) receptor (UT) ligand, [Pen(5),DTrp(7),Dab(8)]U-II(4-11) (UFP-803), was pharmacologically evaluated and compared with urantide in in vitro and in vivo assays. In the rat isolated aorta, UFP-803 was inactive alone but, concentration dependently, displaced the contractile response to U-II to...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0706438
更新日期：2006-01-01 00:00:00
abstract：:1. The role of alpha- and beta-adrenoceptor subtypes in the regulation of plasma glucose and immunoreactive insulin (IRI) levels has been investigated in normal conscious fasted rats by employing selective agonists and antagonists. 2. Adrenaline (0.2 mg kg-1)-induced hyperglycaemia was abolished by the selective alpha...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1990.tb14078.x
更新日期：1990-08-01 00:00:00
abstract：:1 The effects of presynaptic alpha-adrenoceptor blockade on both the efflux of 3H-transmitter and on the magnitude of the effector response were measured simultaneously in a smooth muscle preparation which responds to field stimulation with noradrenergic beta-receptor-mediated relaxation. 2 In the presence of atropine...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1983.tb09386.x
更新日期：1983-01-01 00:00:00
