Abstract:
BACKGROUND AND PURPOSE:Positive modulators of small conductance Ca(2+)-activated K(+) channels (SK1, SK2, and SK3) exert hyperpolarizing effects that influence the activity of excitable and non-excitable cells. The prototype compound 1-EBIO or the more potent compound NS309, do not distinguish between the SK subtypes and they also activate the related intermediate conductance Ca(2+)-activated K(+) channel (IK). This paper demonstrates, for the first time, subtype-selective positive modulation of SK channels. EXPERIMENTAL APPROACH:Using patch clamp and fluorescence techniques we studied the effect of the compound cyclohexyl-[2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine (CyPPA) on recombinant hSK1-3 and hIK channels expressed in HEK293 cells. CyPPA was also tested on SK3 and IK channels endogenously expressed in TE671 and HeLa cells. KEY RESULTS:CyPPA was found to be a positive modulator of hSK3 (EC(50) = 5.6 +/- 1.6 microM, efficacy 90 +/- 1.8 %) and hSK2 (EC(50) = 14 +/- 4 microM, efficacy 71 +/- 1.8 %) when measured in inside-out patch clamp experiments. CyPPA was inactive on both hSK1 and hIK channels. At hSK3 channels, CyPPA induced a concentration-dependent increase in the apparent Ca(2+)-sensitivity of channel activation, changing the EC(50)(Ca(2+)) from 429 nM to 59 nM. CONCLUSIONS AND IMPLICATIONS:As a pharmacological tool, CyPPA may be used in parallel with the IK/SK openers 1-EBIO and NS309 to distinguish SK3/SK2- from SK1/IK-mediated pharmacological responses. This is important for the SK2 and SK1 subtypes, since they have overlapping expression patterns in the neocortical and hippocampal regions, and for SK3 and IK channels, since they co-express in certain peripheral tissues.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Hougaard C,Eriksen BL,Jørgensen S,Johansen TH,Dyhring T,Madsen LS,Strøbaek D,Christophersen Pdoi
10.1038/sj.bjp.0707281subject
Has Abstractpub_date
2007-07-01 00:00:00pages
655-65issue
5eissn
0007-1188issn
1476-5381pii
0707281journal_volume
151pub_type
杂志文章abstract::1 Thermic oedema induced by heating rat paws at 46.5 degrees C was potentiated by local injection of adrenaline, noradrenaline or high doses of isoprenaline. The pro-inflammatory effect of sympathomimetic amines was antagonized by phenoxybenzamine or phentolamine but not by propranolol.2 The subcutaneous space of heat...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1974.tb08568.x
更新日期:1974-02-01 00:00:00
abstract::Mutations in the human melanocortin (MC)4 receptor have been associated with obesity, which underscores the relevance of this receptor as a drug target to treat obesity. Infusion of MC4R agonists decreases food intake, whereas inhibition of MC receptor activity by infusion of an MC receptor antagonist or with the inve...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1038/sj.bjp.0706929
更新日期:2006-12-01 00:00:00
abstract::Vasoactive intestinal peptide (VIP) caused concentration-dependent relaxation in precontracted segments of trachea, hilar bronchus, intrapulmonary bronchus and intrapulmonary artery (IPA) isolated from cat lungs. VIP-induced relaxation responses were abolished by preincubation of tissues with the proteolytic enzyme, a...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1984.tb10766.x
更新日期:1984-06-01 00:00:00
abstract::1. The vasodilator effects of arginine, nitric oxide (NO), acetylcholine (ACh) and sodium nitroprusside (NP) in the noradrenaline-preconstricted ('high tone') perfused rat kidney have been examined. 2. L-Arginine (0.6-23 mumol) caused a biphasic change in renal perfusion pressure. D-Arginine (0.6-23 mumol) was without...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1989.tb12011.x
更新日期:1989-07-01 00:00:00
abstract::1. The endothelium-dependent relaxants acetylcholine (ACh; 0.03-10 microM) and A23187 (0.03-10 microM), and nitric oxide (NO), applied either as authentic NO (0.01-10 microM) or as the NO donors 3-morpholino-sydnonimine (SIN-1; 0.1-10 microM) and S-nitroso-N-acetylpenicillamine (SNAP; 0.1-10 microM), each evoked conce...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701746
更新日期:1998-04-01 00:00:00
abstract::Amyotrophic lateral sclerosis (ALS) is the most common motor neuron neurodegenerative disease. Although it has been classically considered as a disease limited to the motor system, there is increasing evidence for the involvement of other neural and non-neuronal systems. In this review, we will discuss currently exist...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bph.15202
更新日期:2020-07-16 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703356
更新日期:2000-06-01 00:00:00
abstract::1. Skins of the lizard Anolis carolinensis darken in vitro in response to melanophore stimulating hormone (MSH), a peptide hormone, as well as to catecholamines. These hormones darken Anolis skins by dispersing the sub-cellular organelle, the melanosome, out into the dendritic processes of the dermal melanophores.2. D...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1970.tb09565.x
更新日期:1970-05-01 00:00:00
abstract::1. The effect of prostaglandin E1 (PGE1) on the spontaneous phasic contraction of the rat isolated portal vein was studied. 2. The isolated portal vein exhibited spontaneous phasic contractions. Removal of Ca2+ from Krebs-Ringer solution or application of nifedipine abolished the spontaneous contraction, indicating th...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701051
更新日期:1997-04-01 00:00:00
abstract::Prostate cancer is the second most common malignancy in men and androgen deprivation therapy is the first-line therapy. However, most cases will eventually develop castration-resistant prostate cancer after androgen deprivation therapy treatment. Enzalutamide is a second-generation androgen receptor antagonist approve...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bph.15300
更新日期:2020-11-05 00:00:00
abstract:BACKGROUND AND PURPOSE:Pancreatitis represents a life-threatening inflammatory condition where leucocytes, cytokines and vascular endothelium contribute to the development of the inflammatory disease. The glucocorticoid-induced tumour necrosis factor (TNF) receptor family-related protein (GITR) is a costimulatory molec...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2010.01123.x
更新日期:2011-03-01 00:00:00
abstract::1. To investigate the role of nitric oxide in epilepsy we have studied the effects of agents which affect nitric oxide synthesis in sound-induced seizures in DBA/2 mice and in genetically epilepsy-prone (GEP) rats. 2. The neuronal selective nitric oxide synthase inhibitor, 7-nitroindazole (7-NI) is anticonvulsant in t...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb15690.x
更新日期:1996-09-01 00:00:00
abstract::1 The present study comprised treatment of healthy male rats with Delta(9)-tetrahydrocannabinol (THC, 10 mg kg(-1), p.o.), and combinations of THC with benzoflavone moiety (BZF, 10 and 20 mg kg(-1), p.o.) isolated from Passiflora incarnata Linneaus, over a period of 30 days. 2 Upon 30-days chronic administrations, the...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705015
更新日期:2003-01-01 00:00:00
abstract::1. The effects of inhibiting endogenous Cu/Zn superoxide dismutase (SOD) with diethyldithiocarbamate (DETCA) were examined on the ability of hydroquinone, hydroxocobalamin and carboxy-PTIO to block nitrergic relaxation in the bovine retractor penis (BRP) muscle. 2. Incubation of strips of BRP with DETCA (3 mM) for 2 h...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb15333.x
更新日期:1996-04-01 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::In this study we have determined the different signalling pathways involved in adenosine A(1)-receptor (A(1)-receptor)-dependent inhibition of contractility in rat isolated atria. N-cyclopentyladenosine (CPA) stimulation of A(1)-receptor exerts: negative inotropic response, inositol phosphates accumulation, stimulatio...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704487
更新日期:2002-01-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Dysfunction and injury of endothelial cells in the pulmonary artery play critical roles in the hypertension induced by chronic hypoxia. One consequence of hypoxia is increased activity of 15-hydroxyprostaglandin dehydrogenase (PGDH). Here, we have explored, in detail, the effects of hypoxia on th...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.12594
更新日期:2014-07-01 00:00:00
abstract::The muscarinic receptor binding of trazodone, a new nontricyclic antidepressant, was compared with established tricyclic antidepressants. The ability to inhibit the binding of [3H]-quinuclidinyl benzilate in vitro was used for comparing atropine-like effects. Trazodone was found to have essentially no activity at the ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1980.tb10947.x
更新日期:1980-01-01 00:00:00
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doi:10.1111/bph.13386
更新日期:2016-02-01 00:00:00
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doi:10.1111/j.1476-5381.1996.tb15161.x
更新日期:1996-01-01 00:00:00
abstract::1. The ability of the neuroprotective agent, lifarizine (RS-87476), to mitigate veratridine-, cyanide- and glutamate-induced toxicity in rat embryonic cerebrocortical neurones in primary culture has been compared with that of tetrodotoxin (TTX), nitrendipine, (+)-MK-801 and (-)-MK-801. Lactate dehydrogenase (LDH) rele...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb13357.x
更新日期:1995-04-01 00:00:00
abstract::1 4-Aminopyridine methiodide (4-APMI), a quaternary analogue of aminopyridine (4-AP), was tested for neuromuscular facilitatory actions on the chick biventer cervicis and frog sartorius nerve-muscle preparations. 2 In the chick, 4-APMI (10(-4) to 10(-2) M) augmented indirectly elicited twitches and reversed tubocurari...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1979.tb17333.x
更新日期:1979-01-01 00:00:00
abstract::1. The purpose of the present study was to identify and investigate the role of 5-hydroxytryptamine3 (5-HT3) receptors in the area postrema in the control of cisplatin-induced emesis in the ferret. 2. Homogenate binding and autoradiography experiments using the high affinity 5-HT3 receptor ligand, [3H]-GR65630, identi...
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pub_type: 杂志文章
doi:10.1111/j.1476-5381.1989.tb11948.x
更新日期:1989-05-01 00:00:00
abstract::1. 8-Hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), gepirone, buspirone and ipsapirone dose-dependently antagonized the head-shakes induced by 1-(2,5-dimethoxy 4-iodophenyl)-2-amino propane hydrochloride (DOI) (1.0 mg kg-1) in mice, when these agents were given i.p. 10 min beforehand. 2. para-Chlorophenylalanine (...
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pub_type: 杂志文章
doi:10.1111/j.1476-5381.1993.tb13727.x
更新日期:1993-08-01 00:00:00
abstract::The effect of docosahexaenoic acid (DHA) on nitric oxide (NO) production and inducible NO synthase (iNOS) expression induced by interleukin (IL)-1beta, and whether the effect of DHA is related to its effect on mitogen-activated protein kinase (MAPK) activation were investigated in cultured rat vascular smooth muscle c...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704768
更新日期:2002-06-01 00:00:00
abstract::1. Opioid agonists inhibit neurogenic mucus secretion in the airways. The mechanism of the inhibition is unknown but may be via opening of potassium (K+) channels. We studied the effect on neurogenic secretion in ferret trachea in vitro of the OP1 receptor (formerly known as delta opioid receptor) agonist [D-Pen2,5]en...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701786
更新日期:1998-04-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0706341
更新日期:2005-10-01 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:BACKGROUND AND PURPOSE:Non-alcoholic fatty liver disease (NAFLD) is considered to be one of the most common chronic liver diseases across worldwide. Astaxanthin (Ax) is a carotenoid, and beneficial effects of astaxanthin, including anti-oxidative, anti-inflammatory, and anti-tumour activity, have been identified. The p...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.15099
更新日期:2020-08-01 00:00:00
abstract::1. First developed as an antiallergic drug, tranilast inhibits chemical mediator release from mast cells. In the present study, we examine the effects of tranilast on angiogenesis in vitro and in vivo and discuss the application of tranilast for angiogenic diseases. 2. Tranilast inhibited significantly the proliferati...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701493
更新日期:1997-11-01 00:00:00