当前位置： SCI文献检索 > ACTA PHARMACOLOGICA SINICA期刊下所有文献 > Inhibitory effects of lappaconitine on the neuronal isoforms of voltage-gated sodium channels.

Inhibitory effects of lappaconitine on the neuronal isoforms of voltage-gated sodium channels.

Abstract：

:Lappaconitine (LA) has been widely used for postoperative and cancer pain control. LA exhibits excellent analgesic activity with a longer effective time than common local anesthetics such as tetracaine and bupivacaine. However, the mechanisms underlying the featured analgesic activity of LA remain largely unknown. Here, we report that LA is an inhibitor of voltage-gated sodium channel 1.7 (Nav1.7) stably expressed in human embryonic kidney (HEK293) cells. LA inhibited Nav1.7 in a voltage-dependent manner with an IC50 value (with 95% confidence limits) of 27.67 (15.68-39.66) µmol/L when the cell was clamped at -70 mV. In comparison with the quick and reversible inhibition of Nav1.7 by tetracaine and bupivacaine, the inhibitory effect of LA was rather slow and irreversible. It took more than 10 min to achieve steady-state inhibition when LA (300 µmol/L) was administered. Unlike tetracaine and bupivacaine, LA affected neither the voltage-dependent activation nor the inactivation of the channels. Five residues in domain III and domain IV have been reported to be critical for the effects of the two local anesthetics on Nav channels. But our mutant study revealed that only two residues (F1737, N1742) located in domain IV were necessary for the inhibitory activity of LA. The slow onset, irreversibility, and lack of influence on channel activation and inactivation accompanied with the different molecular determinants suggest that LA may inhibit Nav1.7 channels in a manner different from local anesthetics. These results may help to understand the featured analgesic activity of LA, thus benefiting its application in the clinic and future drug development.

journal_name

Acta Pharmacol Sin

journal_title

Acta pharmacologica Sinica

authors

Li YF,Zheng YM,Yu Y,Gan Y,Gao ZB

doi

10.1038/s41401-018-0067-x

subject

Has Abstract

pub_date

2019-04-01 00:00:00

pages

451-459

issue

4

eissn

1671-4083

issn

1745-7254

pii

10.1038/s41401-018-0067-x

journal_volume

40

pub_type

杂志文章

相关文献

ACTA PHARMACOLOGICA SINICA文献大全
  • Quantitative determination of acetylshikonin in macaque monkey blood by LC-ESI-MS/MS after precolumn derivatization with 2-mercaptoethanol and its application in pharmacokinetic study.

    abstract：AIM:To develop and validate a novel precolumn derivatization method for the quantitative determination and pharmacokinetic application of acetylshikonin in macaque monkeys by liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). METHODS:2-Mercaptoethanol was added to the blood sample a...

    journal_title：Acta pharmacologica Sinica

    pub_type： 杂志文章

    doi：10.1111/j.1745-7254.2008.00898.x

    authors： Sun DX,Tian HF,Meng ZY,Du A,Yuan D,Gu RL,Wu ZN,Dou GF

    更新日期：2008-12-01 00:00:00

  • Bevacizumab or fibronectin gene editing inhibits the osteoclastogenic effects of fibroblasts derived from human radicular cysts.

    abstract：:Fibronectin (FN) is a main component of extracellular matrix (ECM) in most adult tissues. Under pathological conditions, particularly inflammation, wound healing and tumors, an alternatively spliced exon extra domain A (EDA) is included in the FN protein (EDA+FN), which facilitates cellular proliferation, motility, an...

    journal_title：Acta pharmacologica Sinica

    pub_type： 杂志文章

    doi：10.1038/s41401-018-0172-x

    authors： Wang HC,Wang P,Chen YW,Zhang Y

    更新日期：2019-07-01 00:00:00

  • Rifampicin induces clathrin-dependent endocytosis and ubiquitin-proteasome degradation of MRP2 via oxidative stress-activated PKC-ERK/JNK/p38 and PI3K signaling pathways in HepG2 cells.

    abstract：:It was reported that antituberculosis medicines could induce liver damage via oxidative stress. In this study, we investigated the effects of rifampicin (RFP) on the membrane expression of multidrug resistance-associated protein 2 (MRP2) and the relationship between oxidative stress and RFP-induced endocytosis of MRP2...

    journal_title：Acta pharmacologica Sinica

    pub_type： 杂志文章

    doi：10.1038/s41401-019-0266-0

    authors： Xu BY,Tang XD,Chen J,Wu HB,Chen WS,Chen L

    更新日期：2020-01-01 00:00:00

  • Affinity of anticancer drug, daunomycin, to core histones in solution: comparison of free and cross-linked proteins.

    abstract：AIM:The interaction of anthracycline anticancer drugs with chromatin, nucleosomes and histone H1 has been extensively studied. In the present study, for the first time, we have investigated the binding of anthracycline antibiotic, daunomycin, to free and cross-linked thymus core histones (CL-core) in solution and in th...

    journal_title：Acta pharmacologica Sinica

    pub_type： 杂志文章

    doi：10.1111/j.1745-7254.2007.00542.x

    authors： Rabbani A,Abdosamadi S,Sari-Saraf N

    更新日期：2007-05-01 00:00:00

  • Recombinant adeno-associated virus-mediated human kallikrein gene therapy protects against hypertensive target organ injuries through inhibiting cell apoptosis.

    abstract：AIM:Overexpression of human tissue kallikrein (HK), mediated by recombinant adeno-associated virus (rAAV), decreased blood pressure in spontaneous hypertensive rats (SHRs) and reduced injury to the heart, aorta and kidney. In this study, we used both an in vivo animal model and in vitro cell culture system to investiga...

    journal_title：Acta pharmacologica Sinica

    pub_type： 杂志文章

    doi：10.1038/aps.2009.114

    authors： Yan JT,Wang T,Wang DW

    更新日期：2009-09-01 00:00:00

  • HIV entry inhibitors: a new generation of antiretroviral drugs.

    abstract：:AIDS is presently treatable, and patients can have a good prognosis due to the success of highly active antiretroviral therapy (HAART), but it is still not curable or preventable. High toxicity of HAART, and the emergence of drug resistance add to the imperative to continue research into new strategies and interventio...

    journal_title：Acta pharmacologica Sinica

    pub_type： 杂志文章,评审

    doi：10.1111/j.1745-7254.2005.00193.x

    authors： Krambovitis E,Porichis F,Spandidos DA

    更新日期：2005-10-01 00:00:00

  • Short hairpin RNA-mediated inhibition of HSV-1 gene expression and function during HSV-1 infection in Vero cells.

    abstract：AIM:To evaluate the efficiency of 3 short hairpin RNA (shRNA) interfering with the herpes simplex virus type 1 (HSV-1) gene coding glycoprotein D (gD) for inhibiting the gD expression and virus replication in vitro. METHODS:Vero cells were selected for an in vitro model of infection. Three shRNA sequences (shRNAgD1, -...

    journal_title：Acta pharmacologica Sinica

    pub_type： 杂志文章

    doi：10.1111/j.1745-7254.2008.00828.x

    authors： Liu YY,Deng HY,Yang G,Jiang WL,Grossin L,Yang ZQ

    更新日期：2008-08-01 00:00:00

  • Activation of muscarinic receptors inhibits glutamate-induced GSK-3β overactivation in PC12 cells.

    abstract：AIM:To investigate the actions of the muscarinic agonist carbachol on glutamate-induced neurotoxicity in PC12 cells, and the underlying mechanisms. METHODS:PC12 cells were treated with different concentrations of glutamate for 24 or 48 h. The cell viability was measured using MTT assay, and the expression and activati...

    journal_title：Acta pharmacologica Sinica

    pub_type： 杂志文章

    doi：10.1038/aps.2013.42

    authors： Ma K,Yang LM,Chen HZ,Lu Y

    更新日期：2013-07-01 00:00:00

  • Reducing fatigue of athletes following oral administration of huangqi jianzhong tang.

    abstract：AIM:To study the effect of Huangqi Jianzhong Tang in reducing fatigue improvement in athletes. METHODS:Twelve athletes were randomly separated into a control group, whose members were administered with placebos, and the experimental group, whose members were administered with Huangqi Jianzhong Tang. During the eight w...

    journal_title：Acta pharmacologica Sinica

    pub_type： 临床试验,杂志文章,随机对照试验

    doi：

    authors： Chen KT,Su CH,Hsin LH,Su YC,Su YP,Lin JG

    更新日期：2002-08-01 00:00:00

  • Pathogenic roles of microvesicles in diabetic retinopathy.

    abstract：:Diabetic retinopathy (DR) is a common complication of diabetes and has been recognized as the leading cause of blindness in adults. Several interrelated molecular pathways are involved in the development of DR. Microvesicles (MVs) are cell membrane vesicles, which carry many biologic molecules, such as mRNAs, microRNA...

    journal_title：Acta pharmacologica Sinica

    pub_type： 杂志文章,评审

    doi：10.1038/aps.2017.77

    authors： Zhang W,Chen S,Liu ML

    更新日期：2018-01-01 00:00:00

  • Effect of unsaturated fatty acid on muscarinic current in guinea pig gastric antral circular myocytes.

    abstract：AIM:To investigate the effect of ectogenesis unsaturated fatty acid on carbachol-induced muscarinic current (ICCh) and its mechanism. METHODS:Using the whole-cell patch-clamp technique, ICCh was recorded in single smooth muscle cell isolated from the antral circular smooth muscles of guinea-pig stomach. RESULTS:Arach...

    journal_title：Acta pharmacologica Sinica

    pub_type： 杂志文章

    doi：

    authors： Cui YF,Jin H,Guo HS,Li L,Yu YC,Xu WX

    更新日期：2003-03-01 00:00:00

  • Expression of angiopoietin-2 and vascular endothelial growth factor in mice cerebral cortex after permanent focal cerebral ischemia.

    abstract：AIM:To study the expressions of vascular endothelial growth factor (VEG F), angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), Tie-1, and Tie-2 in C57BL/6 mouse brain after permanent focal cerebral ischemia. METHODS:The mRNA levels of VEGF, Ang-1, Ang-2, Tie-1, and Tie-2 were measured by semiquantitative reverse transcri...

    journal_title：Acta pharmacologica Sinica

    pub_type： 杂志文章

    doi：

    authors： Wang RG,Zhu XZ

    更新日期：2002-05-01 00:00:00

  • DW10075, a novel selective and small-molecule inhibitor of VEGFR, exhibits antitumor activities both in vitro and in vivo.

    abstract：AIM:Targeting the VEGF/VEGF receptor (VEGFR) pathway has proved to be an effective antiangiogenic approach for cancer treatment. Here, we identified 6-((2-((3-acetamidophenyl)amino)pyrimidin-4-yl)oxy)-N-phenyl-1-naphthamide (designated herein as DW10075) as a novel and highly selective inhibitor of VEGFRs. METHODS:In ...

    journal_title：Acta pharmacologica Sinica

    pub_type： 杂志文章

    doi：10.1038/aps.2015.117

    authors： Li MY,Lv YC,Tong LJ,Peng T,Qu R,Zhang T,Sun YM,Chen Y,Wei LX,Geng MY,Duan WH,Xie H,Ding J

    更新日期：2016-03-01 00:00:00

  • Matrine pretreatment improves cardiac function in rats with diabetic cardiomyopathy via suppressing ROS/TLR-4 signaling pathway.

    abstract：AIM:Matrine is an alkaloid from Sophora alopecuroides L, which has shown a variety of pharmacological activities and potential therapeutic value in cardiovascular diseases. In this study we examined the protective effects of matrine against diabetic cardiomyopathy (DCM) in rats. METHODS:Male SD rats were injected with...

    journal_title：Acta pharmacologica Sinica

    pub_type： 杂志文章

    doi：10.1038/aps.2014.127

    authors： Liu ZW,Wang JK,Qiu C,Guan GC,Liu XH,Li SJ,Deng ZR

    更新日期：2015-03-01 00:00:00

  • Diosgenin relieves goiter via the inhibition of thyrocyte proliferation in a mouse model of Graves' disease.

    abstract：AIM:To investigate the effects of diosgenin (Dio), a naturally occurring steroid saponin, on goiter formation in a mouse model of Graves' disease (GD) and the underlying mechanisms. METHODS:Female BALB/c mice were injected with adenovirus expressing the A subunit of thyrotropin receptor to induce GD. The mice were tre...

    journal_title：Acta pharmacologica Sinica

    pub_type： 杂志文章

    doi：10.1038/aps.2013.133

    authors： Cai H,Wang Z,Zhang HQ,Wang FR,Yu CX,Zhang FX,Gao L,Zhang J,Zhao JJ

    更新日期：2014-01-01 00:00:00

  • Enhancement of binding activity of soluble human CD40 to CD40 ligand through incorporation of an isoleucine zipper motif.

    abstract：AIM:To investigate the effect of incorporation of an isoleucine zipper (IZ) motif into CD40 on binding activity of CD40 for the CD40 ligand (CD40L). METHODS:Prokaryotic expression vectors for 2 soluble CD40 derivatives, shCD40His and shCD40IZ containing an IZ domain, were constructed and expressed in Escherichia coli....

    journal_title：Acta pharmacologica Sinica

    pub_type： 杂志文章

    doi：10.1111/j.1745-7254.2006.00285.x

    authors： He XH,Xu LH,Liu Y

    更新日期：2006-03-01 00:00:00

  • Salvianolic acid A attenuates vascular remodeling in a pulmonary arterial hypertension rat model.

    abstract：AIM:The current therapeutic approaches have a limited effect on the dysregulated pulmonary vascular remodeling, which is characteristic of pulmonary arterial hypertension (PAH). In this study we examined whether salvianolic acid A (SAA) extracted from the traditional Chinese medicine 'Dan Shen' attenuated vascular remo...

    journal_title：Acta pharmacologica Sinica

    pub_type： 杂志文章

    doi：10.1038/aps.2016.22

    authors： Chen YC,Yuan TY,Zhang HF,Wang DS,Yan Y,Niu ZR,Lin YH,Fang LH,Du GH

    更新日期：2016-06-01 00:00:00

  • Chip-based digital PCR as a novel detection method for quantifying microRNAs in acute myocardial infarction patients.

    abstract：:miRNAs have shown promise as potential biomarkers for acute myocardial infarction (AMI). However, the current used quantitative real-time PCR (qRT-PCR) allows solely for relative expression of nucleic acids and it is susceptible to day-to-day variability, which has limited the validity of using the miRNAs as biomarker...

    journal_title：Acta pharmacologica Sinica

    pub_type： 杂志文章

    doi：10.1038/aps.2017.136

    authors： Robinson S,Follo M,Haenel D,Mauler M,Stallmann D,Heger LA,Helbing T,Duerschmied D,Peter K,Bode C,Ahrens I,Hortmann M

    更新日期：2018-07-01 00:00:00

  • FTY720, a new immunosuppressant, as rescue therapy in mouse cardiac transplantation.

    abstract：AIM:FTY720 is a new synthetic immunosuppressive agent which has a unique mechanism of action and induces long-term graft acceptance in rat and dog allotransplantation as prophylactic administration. The present study investigated whether FTY720 was able to rescue ongoing acute rejection of solid organ transplants in a ...

    journal_title：Acta pharmacologica Sinica

    pub_type： 杂志文章

    doi：

    authors： Wang MH,Milekhin V,Zhang H,Huang HZ

    更新日期：2003-09-01 00:00:00

  • The effect of pinacidil on postshock activation and ventricular defibrillation threshold in canine hearts.

    abstract：AIM:To determine the postshock activation patterns with both successful and failed shocks in a canine model of ventricular fibrillation, and whether piniacidil, an early after-depolarization (EAD) inhibitor, altered the defibrillation threshold (DFT) and postshock activation patterns. METHODS:In 6 beagles, a basket ca...

    journal_title：Acta pharmacologica Sinica

    pub_type： 杂志文章

    doi：10.1038/aps.2012.96

    authors： Jin Q,Zhang N,Zhou J,Lin CJ,Pang Y,Gu G,Shen WF,Wu LQ

    更新日期：2012-12-01 00:00:00

  • Growth suppression and radiosensitivity increase by HMGB1 in breast cancer.

    abstract：AIM:HMGB1 (high-mobility group box-1) is a nuclear protein containing a consensus RB (retinoblastoma)-binding LXCXE motif. In this study, we studied the potential association of HMGB1 and RB and the in vitro and in vivo activities of HMGB1 in human breast cancer cells. METHODS:The protein-protein interaction was deter...

    journal_title：Acta pharmacologica Sinica

    pub_type： 杂志文章

    doi：10.1111/j.1745-7254.2007.00669.x

    authors： Jiao Y,Wang HC,Fan SJ

    更新日期：2007-12-01 00:00:00

  • Hyposmotic challenge modulates function of L-type calcium channel in rat ventricular myocytes through protein kinase C.

    abstract：AIM:To study the effects and mechanisms by which hyposmotic challenge modulate function of L-type calcium current (I(Ca,L)) in rat ventricular myocytes. METHODS:The whole-cell patch-clamp techniques were used to record I(Ca,L) in rat ventricular myocytes. RESULTS:Hyposmotic challenge(∼220 mosmol/L) induced biphasic c...

    journal_title：Acta pharmacologica Sinica

    pub_type： 杂志文章

    doi：10.1038/aps.2010.112

    authors： Luo AT,Luo HY,Hu XW,Gao LL,Liang HM,Tang M,Hescheler J

    更新日期：2010-11-01 00:00:00

  • SHR-A1403, a novel c-Met antibody-drug conjugate, exerts encouraging anti-tumor activity in c-Met-overexpressing models.

    abstract：:Emerging evidence demonstrates that a c-Met antibody-drug conjugate (ADC) has superior efficacy and safety profiles compared with those of currently available small molecules or antibody inhibitors for the treatment of c-Met-overexpressing cancers. Here we described both the in vitro and in vivo efficacies of SHR-A140...

    journal_title：Acta pharmacologica Sinica

    pub_type： 杂志文章

    doi：10.1038/s41401-018-0198-0

    authors： Yang CY,Wang L,Sun X,Tang M,Quan HT,Zhang LS,Lou LG,Gou SH

    更新日期：2019-07-01 00:00:00

  • Wound healing activity of human placental extracts in rats.

    abstract：AIM:To study wound healing activity of the human placental extract (HPE) in rats. METHODS:Full thickness wounds were inflicted on depilated dorsum of Charles foster rats with 8 mm Acu-punch biopsy. The HPE was applied both at topical and im routes (2.5 mL/kg). Effects were compared on the basis of physical criteria, b...

    journal_title：Acta pharmacologica Sinica

    pub_type： 杂志文章

    doi：

    authors： Biswas TK,Auddy B,Bhattacharya NP,Bhattacharya S,Mukherjee B

    更新日期：2001-12-01 00:00:00

  • Effects of linagliptin and liraglutide on glucose- and angiotensin II-induced collagen formation and cytoskeleton degradation in cardiac fibroblasts in vitro.

    abstract：AIM:Glucagon-like peptide-1 (GLP-1) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors can not only lower blood glucose levels, but also alleviate cardiac remodeling after myocardial ischemia and hypertension. In the present study, we investigated the effects of a DPP-4 inhibitor (linagliptin) and a GLP-1 activator...

    journal_title：Acta pharmacologica Sinica

    pub_type： 杂志文章

    doi：10.1038/aps.2016.72

    authors： Wang XW,Zhang FX,Yang F,Ding ZF,Agarwal N,Guo ZK,Mehta JL

    更新日期：2016-09-01 00:00:00

  • Pentoxifylline alleviates high-fat diet-induced non-alcoholic steatohepatitis and early atherosclerosis in rats by inhibiting AGE and RAGE expression.

    abstract：AIM:To investigate the expression of advanced glycation end products (AGEs) and their receptor RAGE in the livers and blood vessels of rats with non-alcoholic steatohepatitis (NASH) and the effect of pentoxifylline (PTX) on liver and artery function in rats with NASH. METHODS:Sprague-Dawley rats were fed a high-fat di...

    journal_title：Acta pharmacologica Sinica

    pub_type： 杂志文章

    doi：10.1038/aps.2010.110

    authors： Wu J,Zhao MY,Zheng H,Zhang H,Jiang Y

    更新日期：2010-10-01 00:00:00

  • Beneficial effects of melatonin in experimental models of Alzheimer disease.

    abstract：:Alzheimer's disease (AD), a progressive degenerative disorder, is characterized by the presence of amyloid deposits, neurofibrillary tangles and neuron loss. Emerging evidence indicates that antioxidants could be useful either for the prevention or treatment of AD. It has been shown that melatonin is a potent antioxid...

    journal_title：Acta pharmacologica Sinica

    pub_type： 杂志文章,评审

    doi：10.1111/j.1745-7254.2006.00267.x

    authors： Cheng Y,Feng Z,Zhang QZ,Zhang JT

    更新日期：2006-02-01 00:00:00

  • Development of a high-throughput fluorescence polarization assay for the discovery of EZH2-EED interaction inhibitors.

    abstract：:Aberrant activity of enhancer of zeste homolog 2 (EZH2) is associated with a wide range of human cancers. The interaction of EZH2 with embryonic ectoderm development (EED) is required for EZH2's catalytic activity. Inhibition of the EZH2-EED complex thus represents a novel strategy for interfering with the oncogenic p...

    journal_title：Acta pharmacologica Sinica

    pub_type： 杂志文章

    doi：10.1038/aps.2017.59

    authors： Zhu MR,Du DH,Hu JC,Li LC,Liu JQ,Ding H,Kong XQ,Jiang HL,Chen KX,Luo C

    更新日期：2018-02-01 00:00:00

  • Role of calcitonin gene-related peptide in nitric oxide-mediated myocardial delayed preconditioning induced by head stress.

    abstract：AIM:To study the role of calcitonin gene-related peptide (CGRP) in nitric oxide (NO)-mediated myocardial delayed preconditioning induced by heat stress. METHODS:The isolated rat heart was perfused in a Langendorff model. Hearts for all groups were subjected to 4 h hypothermia (4 degrees C) and 40 min reperfusion (37 d...

    journal_title：Acta pharmacologica Sinica

    pub_type： 杂志文章

    doi：

    authors： Tan B,He SY,Deng HW,Li YJ

    更新日期：2001-09-01 00:00:00

  • Resveratrol protects bone marrow mesenchymal stem cell derived chondrocytes cultured on chitosan-gelatin scaffolds from the inhibitory effect of interleukin-1beta.

    abstract：AIM:To investigate the effects of resveratrol on interleukin-1beta (IL-1beta) induced catabolism in bone marrow mesenchymal stem cell (MSC) derived chondrocytes cultured on chitosan-gelatin scaffolds (CGS). METHODS:The chondrogenesis of alginate-encapsulated MSCs was evaluated by toluidine blue staining, RT-PCR, and i...

    journal_title：Acta pharmacologica Sinica

    pub_type： 杂志文章

    doi：10.1111/j.1745-7254.2008.00880.x

    authors： Lei M,Liu SQ,Liu YL

    更新日期：2008-11-01 00:00:00