Abstract：
BACKGROUND AND PURPOSE:Methylene blue (MB) is commonly employed as a treatment for methaemoglobinaemia, malaria and vasoplegic shock. An increasing number of studies indicate that MB can cause 5-HT toxicity when administered with a 5-HT reuptake inhibitor. MB is a potent inhibitor of monoamine oxidases, but other targets that may contribute to MB toxicity have not been identified. Given the role of the 5-HT transporter (SERT) in the regulation of extracellular 5-HT concentrations, the present study aimed to characterize the effect of MB on SERT. EXPERIMENTAL APPROACH:Live cell imaging, in conjunction with the fluorescent SERT substrate 4-(4-(dimethylamino)-styryl)-N-methylpyridinium (ASP(+) ), [(3) H]5-HT uptake and whole-cell patch-clamp techniques were employed to examine the effects of MB on SERT function. KEY RESULTS:In EM4 cells expressing GFP-tagged human SERT (hSERT), MB concentration-dependently inhibited ASP(+) accumulation (IC(50) : 1.4 ± 0.3 µM). A similar effect was observed in N2A cells. Uptake of [(3) H]5-HT was decreased by MB pretreatment. Furthermore, patch-clamp studies in hSERT expressing cells indicated that MB significantly inhibited 5-HT-evoked ion currents. Pretreatment with 8-Br-cGMP did not alter the inhibitory effect of MB on hSERT activity, and intracellular Ca(2+) levels remained unchanged during MB application. Further experiments revealed that ASP(+) binding to cell surface hSERT was reduced after MB treatment. In whole-cell radioligand experiments, exposure to MB (10 µM; 10 min) did not alter surface binding of the SERT ligand [(125) I]RTI-55. CONCLUSIONS AND IMPLICATIONS:MB modulated SERT function and suggested that SERT may be an additional target upon which MB acts to produce 5-HT toxicity.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Oz M,Isaev D,Lorke DE,Hasan M,Petroianu G,Shippenberg TSdoi
10.1111/j.1476-5381.2011.01462.xsubject
Has Abstractpub_date
2012-05-01 00:00:00pages
168-76issue
1eissn
0007-1188issn
1476-5381journal_volume
166pub_type
杂志文章abstract：BACKGROUND AND PURPOSE:Cigarette smoke is a major cause for chronic obstructive pulmonary disease (COPD). Andrographolide is an active biomolecule isolated from the plant Andrographis paniculata. Andrographolide has been shown to activate nuclear factor erythroid-2-related factor 2 (Nrf2), a redox-sensitive antioxidant...
journal_title：British journal of pharmacology
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doi：10.1111/bph.12054
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abstract：:1. Prostaglandins and the vasodilator neuropeptide, calcitonin-gene related peptide (CGRP), have both been implicated in the pathogenesis of migraine headache. We have used primary cultures of adult rat trigeminal neurones to examine the effects of prostanoids on CGRP release in vitro. 2. CGRP release was stimulated b...
journal_title：British journal of pharmacology
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doi：10.1038/sj.bjp.0704357
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journal_title：British journal of pharmacology
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doi：10.1111/j.1476-5381.1971.tb07220.x
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abstract：:1. The present study was undertaken to determine the mechanism of action of endothelin-1 (ET-1)-induced contraction of the guinea-pig isolated trachea. 2. ET-1 (1 nM-0.3 microM) produces a concentration-dependent contraction of guinea-pig trachea with an EC50 of approximately 25 nM. The combination of the peptidoleuko...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1993.tb13906.x
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abstract：:Class A1 scavenger receptors (SR-A1) are membrane glycoproteins that can form homotrimers. This receptor was originally defined by its ability to mediate the accumulation of lipids in macrophages. Subsequent studies reveal that SR-A1 plays critical roles in innate immunity, cell apoptosis and proliferation. This revie...
journal_title：British journal of pharmacology
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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
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abstract：:The cardiovascular actions of cannbinoids are complex. In general they cause vasorelaxation in isolated blood vessels, while in anaesthetised animals they cause multiphasic responses which involve an early bradycardia and long-lasting hypotension. However, in conscious animals, the picture is one of bradycardia follow...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
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abstract：:1. The study was designed to test the hypothesis that nitric oxide (NO)-releasing compounds increase guanosine 3':5'-cyclic monophosphate (cyclic GMP) production in human polymorphonuclear leucocytes (PMNs) and concomitantly inhibit PMN functions, i.e. leukotriene B4 (LTB4) synthesis, degranulation, chemotaxis and sup...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1993.tb13653.x
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abstract：:1. The present study was undertaken to investigate the anti-inflammatory effects of a synthetic compound, LCY-2-CHO, on the expression of inducible nitric oxide synthase (iNOS), COX-2, and TNF-alpha in murine RAW264.7 macrophages. 2. Within 1-30 microm, LCY-2-CHO concentration-dependently inhibited lipopolysaccharide ...
journal_title：British journal of pharmacology
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1986.tb10179.x
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abstract：:1 About 45% of singly-housed male mice showed timidity (alert postures, running away, defensive postures) instead of aggression on interactions in pairs with group-housed male mice, though their partners did not show any aggression. The isolation-induced timidity was stable in repeated interactions. Timid mice also sh...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1975.tb07622.x
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abstract：:[3H]-guanfacine (N-amidino-2-(2,6-dichloro 3[3H] phenyl) acetamide hydrochloride; 24.2 Ci/mmol) has been used as a radioligand in homogenates of rat cerebral cortex. Specific binding of [3H]-guanfacine was linear with respect to tissue concentration (2.5-15 mg/ml), saturable and not markedly affected in the pH range 6...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1982.tb08801.x
更新日期：1982-02-01 00:00:00
abstract：:1. The effects of intracameral injections of prostaglandins E(1), E(2), F(1a), F(2a), and A(1) were studied on the intraocular pressure (IOP) of rabbits anaesthetized with urethane.2. With the exception of prostaglandin F(1a), all the prostaglandins studied were found to be capable of producing a large, sustained rise...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1969.tb09533.x
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abstract：:1 The effects of a subconstrictor dose of histamine (9 x 10(-7) mol/l) on the responses of the isolated perfused ear artery of the rabbit to electrical stimulation (E.S.) and to exogenous noradrenaline (NA) were investigated.2 Both intraluminal (I/L) and extraluminal (E/L) histamine potentiated responses to E.S. and t...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1979.tb08684.x
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abstract：:1. Membrane effects of cromakalim (Crom; 50-300 microM) were examined in CA1 neurones recorded mainly by intracellular, single-electrode voltage-clamping in slices (from Sprague-Dawley rats) kept in an interface chamber at 33 degrees C. 2. In 14 cells held at -63 +/- 3.5 mV, in the presence of tetrodotoxin, kynurenic ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1994.tb17004.x
更新日期：1994-10-01 00:00:00
abstract：BACKGROUND AND PURPOSE:β-Adrenoceptor stimulation induces glucose uptake in several insulin-sensitive tissues by poorly understood mechanisms. EXPERIMENTAL APPROACH:We used a model system in CHO-K1 cells expressing the human β(2)-adrenoceptor and glucose transporter 4 (GLUT4) to investigate the signalling mechanisms i...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2011.01647.x
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abstract：BACKGROUND AND PURPOSE:Marijuana smoking is widespread in many countries, and the use of smoked synthetic cannabinoids is increasing. Smoking a marijuana joint leads to bronchodilation in both healthy subjects and asthmatics. The effects of Δ(9) -tetrahydrocannabinol and synthetic cannabinoids on human bronchus reactiv...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.12597
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pub_type： 杂志文章
doi：10.1111/j.1476-5381.1981.tb09986.x
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doi：10.1111/j.1476-5381.1975.tb07569.x
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abstract：:1. Pressor responses to sympathetic outflow stimulation, noradrenaline and angiotensin have been recorded in pithed rats.2. Disulfiram (50 mg/kg) and sodium diethyldithiocarbamate (DDC) (5-100 mg/kg) both caused an initial increase in the pressor response to all three procedures followed by a selective inhibition of t...
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abstract：:1 gamma-Aminobutyric acid (GABA, 0.1 to 1 mM) had no significant effect on the amplitude, rise time, half decay time or frequency of miniature endplate potentials (m.e.p.ps) at the frog or mouse neuromuscular junctions in vitro. 2 Addition of GABA (1 mM) to preparations previously treated with 11 mM K+-Ringer did not ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
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更新日期：1980-01-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Although picrotoxin is a well-established antagonist of GABA(A) receptors, detailed studies of its action on inhibitory synaptic transmission have not previously been made. EXPERIMENTAL APPROACH:Electrophysiological techniques were used to study the action of picrotoxin on inhibitory postsynapti...
journal_title：British journal of pharmacology
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doi：10.1111/j.1476-5381.2009.00542.x
更新日期：2010-02-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Emesis is a multi-system reflex, which is usually investigated using in vivo models. The aim of the study is to compare the response induced by emetic compounds across species and investigate whether dogs, ferrets and rats are all similarly predictive of humans. EXPERIMENTAL APPROACH:A systemati...
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pub_type： 杂志文章,评审
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更新日期：2012-03-01 00:00:00
