In vitro metabolic characteristics of cytochrome P-450 2A6 in Chinese liver microsomes.

Abstract:

AIM:To investigate the metabolic characteristics of cytochrome P-450 C YP2A6 in human liver microsomes. METHODS:Cytochrome P-450 enzyme activities were measured by biochemical assays. Xenobiotics were employed to observe their effects on CYP2A6 in vitro. The kinetics of coumarin 7-hydroxylase was determined, and the correlation between CYP2A6 and UDP-glucuronosyltransferase (UGT) was analyzed. RESULTS:CYP2A6 activities of human liver microsomes were from 0.47 to 4.14 micromol . min-1 . g-1, with a 8.8-fold variation. The Km and Vmax of CYP2A6 ranged from 0.25 to 1.56 micromol/L and 1.41 to 8.70 micromol . min-1 . g-1, respectively. CYP2A6 activity was markedly inhibited (> 50 %) by pilocarpine, diethyldithio carbamic (DDC), and rifampicin, the IC50 was 5.31 micromol/L, 156.35 micromol/L, and 38.81 micromol/L, respectively. alpha-Naphthoflavone, sulfaphenazole, troleandomycin (TAO), ketoconazole, phenobarbital, prednisolone, and azithromycin had little or no effects on coumarin 7-hydroxylation. A significant correlation was observed between CYP2A6 and UGT2 (r = 0.9453, P < 0.05). CONCLUSION:CYP2A6 activity and kinetics exhibited a considerable variation in human liver microsomes in vitro, and a significant correlation was existed between CYP2A6 and phase II enzyme UGT2. Not only pilocarpine, CYP2A6 specific inhibitor, but also rifampicin and DDC inhibited CYP2A6 activity selectively.

journal_name

Acta Pharmacol Sin

authors

Xia XY,Peng RX,Yu JP,Wang H,Wang J

subject

Has Abstract

pub_date

2002-05-01 00:00:00

pages

471-6

issue

5

eissn

1671-4083

issn

1745-7254

journal_volume

23

pub_type

杂志文章
  • Sodium butyrate and dexamethasone promote exocrine pancreatic gene expression in mouse embryonic stem cells.

    abstract:AIM:The feasibility of inducing endocrine pancreatic differentiation of embryonic stem (ES) cells has been well documented. However, whether ES cells possess the potential for exocrine pancreatic differentiation requires further exploration. Here, we investigated whether sodium butyrate and glucocorticoids were conduci...

    journal_title:Acta pharmacologica Sinica

    pub_type: 杂志文章

    doi:10.1038/aps.2009.115

    authors: Ren M,Yan L,Shang CZ,Cao J,Li FP,Li JY,Cheng H,Min J

    更新日期:2009-09-01 00:00:00

  • Sevoflurane postconditioning protects against myocardial ischemia/reperfusion injury by restoring autophagic flux via an NO-dependent mechanism.

    abstract::Volatile anesthetics improve postischemic cardiac function and reduce infarction even when administered for only a brief time at the onset of reperfusion. A recent study showed that sevoflurane postconditioning (SPC) attenuated myocardial reperfusion injury, but the underlying mechanisms remain unclear. In this study,...

    journal_title:Acta pharmacologica Sinica

    pub_type: 杂志文章

    doi:10.1038/s41401-018-0066-y

    authors: Qiao SG,Sun Y,Sun B,Wang A,Qiu J,Hong L,An JZ,Wang C,Zhang HL

    更新日期:2019-01-01 00:00:00

  • Cellular mechanism for spontaneous calcium oscillations in astrocytes.

    abstract:AIM:To determine the Ca2+ source and cellular mechanisms of spontaneous Ca2+ oscillations in hippocampal astrocytes. METHODS:The cultured cells were loaded with Fluo-4 AM, the indicator of intracellular Ca2+, and the dynamic Ca2+ transients were visualized with confocal laser-scanning microscopy. RESULTS:The spontane...

    journal_title:Acta pharmacologica Sinica

    pub_type: 杂志文章

    doi:10.1111/j.1745-7254.2006.00397.x

    authors: Wang TF,Zhou C,Tang AH,Wang SQ,Chai Z

    更新日期:2006-07-01 00:00:00

  • Urotensin II accelerates cardiac fibrosis and hypertrophy of rats induced by isoproterenol.

    abstract:AIM:To study whether urotensin II (UII), a potent vasoconstrictive peptide, is involved in the development of cardiac hypertrophy and fibrogenesis of rats induced by isoproterenol (ISO). METHODS:Thirty male Wistar rats were randomly divided into 3 groups. Group 1 was the healthy control group, group 2 was the ISO grou...

    journal_title:Acta pharmacologica Sinica

    pub_type: 杂志文章

    doi:10.1111/j.1745-7254.2007.00485.x

    authors: Zhang YG,Li YG,Liu BG,Wei RH,Wang DM,Tan XR,Bu DF,Pang YZ,Tang CS

    更新日期:2007-01-01 00:00:00

  • Regulation of the nongenomic actions of retinoid X receptor-α by targeting the coregulator-binding sites.

    abstract::Retinoid X receptor-α (RXRα), a unique member of the nuclear receptor superfamily, represents an intriguing and unusual target for pharmacologic interventions and therapeutic applications in cancer, metabolic disorders and neurodegenerative diseases. Despite the fact that the RXR-based drug Targretin (bexarotene) is c...

    journal_title:Acta pharmacologica Sinica

    pub_type: 杂志文章,评审

    doi:10.1038/aps.2014.109

    authors: Zhang XK,Su Y,Chen L,Chen F,Liu J,Zhou H

    更新日期:2015-01-01 00:00:00

  • The residue I257 at S4-S5 linker in KCNQ1 determines KCNQ1/KCNE1 channel sensitivity to 1-alkanols.

    abstract:AIM:KCNQ1 and KCNE1 form a complex in human ventricular cardiomyocytes, which are important in maintaining a normal heart rhythm. In the present study we investigated the effects of a homologous series of 1-alkanols on KCNQ1/KCNE1 channels expressed in Xenopus oocytes. METHODS:ECG recording was made in rats injected w...

    journal_title:Acta pharmacologica Sinica

    pub_type: 杂志文章

    doi:10.1038/aps.2015.133

    authors: Xie C,Liu HW,Pan N,Ding JP,Yao J

    更新日期:2016-01-01 00:00:00

  • Anisomycin induces glioma cell death via down-regulation of PP2A catalytic subunit in vitro.

    abstract:AIM:To examine the effects of anisomycin on glioma cells and the related mechanisms in vitro. METHODS:The U251 and U87 human glioblastoma cell lines were tested. The growth of the cells was analyzed using a CCK-8 cell viability assay. Apoptosis was detected using a flow cytometry assay. The expression of proteins and ...

    journal_title:Acta pharmacologica Sinica

    pub_type: 杂志文章

    doi:10.1038/aps.2012.46

    authors: Li JY,Huang JY,Li M,Zhang H,Xing B,Chen G,Wei D,Gu PY,Hu WX

    更新日期:2012-07-01 00:00:00

  • High-throughput real-time assay based on molecular beacons for HIV-1 integrase 3'-processing reaction.

    abstract:AIM:To develop a high-throughput real-time assay based on molecular beacons to monitor the integrase 3'-processing reaction in vitro and apply it to inhibitor screening. METHODS:The recombinant human immunodeficiency virus (HIV)-1 integrase (IN) is incubated with a 38 mer oligonucleotide substrate, a sequence identica...

    journal_title:Acta pharmacologica Sinica

    pub_type: 杂志文章

    doi:10.1111/j.1745-7254.2007.00561.x

    authors: He HQ,Ma XH,Liu B,Zhang XY,Chen WZ,Wang CX,Cheng SH

    更新日期:2007-06-01 00:00:00

  • Hypoxia, HIF-1α, and COVID-19: from pathogenic factors to potential therapeutic targets.

    abstract::The pandemic of coronavirus disease 2019 (COVID-19) and its pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have become the greatest current threat to global public health. The highly infectious SARS-CoV-2 virus primarily attacks pulmonary tissues and impairs gas exchange leading to acute respir...

    journal_title:Acta pharmacologica Sinica

    pub_type: 杂志文章,评审

    doi:10.1038/s41401-020-00554-8

    authors: Serebrovska ZO,Chong EY,Serebrovska TV,Tumanovska LV,Xi L

    更新日期:2020-12-01 00:00:00

  • Selective ligands of estrogen receptor β discovered using pharmacophore mapping and structure-based virtual screening.

    abstract:AIM:To discover novel ligands of estrogen receptor (ER) β using pharmacophore mapping and structure-based screening. METHODS:A computer-aided strategy combining pharmacophore mapping and structure-based screening was used to screen the Maybridge and Enamine databases. Yeast two-hybrid (Y2H) assay was used to detect th...

    journal_title:Acta pharmacologica Sinica

    pub_type: 杂志文章

    doi:10.1038/aps.2014.69

    authors: Chen L,Wu D,Bian HP,Kuang GL,Jiang J,Li WH,Liu GX,Zou SE,Huang J,Tang Y

    更新日期:2014-10-01 00:00:00

  • Conformational flexibility of beta-secretase: molecular dynamics simulation and essential dynamics analysis.

    abstract:AIM:Based on the structural analysis to reveal the mechanism of ligand binding to beta-secretase and the specificity of each binding sub-site. METHODS:Molecular dynamics was used to simulate on the ligand free beta-secretase and ligand bound beta-secretase. The trajectories were analyzed using the essential dynamics, ...

    journal_title:Acta pharmacologica Sinica

    pub_type: 杂志文章

    doi:

    authors: Xiong B,Huang XQ,Shen LL,Shen JH,Luo XM,Shen X,Jiang HL,Chen KX

    更新日期:2004-06-01 00:00:00

  • Computational insights into the subtype selectivity and "message-address-efficacy" mechanisms of opioid receptors through JDTic binding and unbinding.

    abstract::In drug design and discovery, binding affinity and selectivity are two basic properties of a drug candidate. Opioid receptors (ORs) are the main targets of strong analgesics. Like some other class A members of G-protein-coupled receptors (GPCRs), ORs exhibit complex selectivity on their ligands. The diversity of bindi...

    journal_title:Acta pharmacologica Sinica

    pub_type: 杂志文章

    doi:10.1038/aps.2017.132

    authors: Cheng JX,Cheng T,Li WH,Liu GX,Zhu WL,Tang Y

    更新日期:2018-03-01 00:00:00

  • Protective effects of apocynin on "two-hit" injury induced by hemorrhagic shock and lipopolysaccharide.

    abstract:AIM:To evaluate the protective effects of apocynin on "two-hit" injury in rats. METHODS:"Two-hit" injury model of rat was induced by hemorrhagic shock (40 mmHg for 45 min) followed by iv administration of lipopolysaccharide (LPS, 150 microg/kg). Rats were randomized into seven groups: Sham, LPS, hemorrhage, hemorrhage...

    journal_title:Acta pharmacologica Sinica

    pub_type: 杂志文章

    doi:

    authors: Zhou R,Hu DY,Liu LM,Zhou XW

    更新日期:2002-11-01 00:00:00

  • Angiotensin II type 2 receptor gene polymorphisms and essential hypertension.

    abstract:AIM:To identify the genetic variants of angiotensin II type 2 receptor (AT2R) gene in a Chinese population and to determine whether the AT2R gene polymorphisms are associated with essential hypertension (EH). METHODS:The detection of single nucleotide polymorphisms (SNPs) was performed in 19 subjects by a direct DNA s...

    journal_title:Acta pharmacologica Sinica

    pub_type: 杂志文章

    doi:

    authors: Zhang Y,Zhang KX,Wang GL,Huang W,Zhu DL

    更新日期:2003-11-01 00:00:00

  • Cardiac toxicity of resibufogenin: electrophysiological evidence.

    abstract::Resibufogenin (RBG) is a single compound isolated from Chansu, a traditional Chinese medicine obtained from the skin venom gland of the toad. Formulations of Chansu have been widely applied in China, Japan, and other Asian countries for a long time and are currently used as alternative medicines. However, there have b...

    journal_title:Acta pharmacologica Sinica

    pub_type: 杂志文章,评审

    doi:

    authors: Xie JT,Dey L,Wu JA,Lowell TK,Yuan CS

    更新日期:2001-04-01 00:00:00

  • Carbachol inhibits TNF-α-induced endothelial barrier dysfunction through alpha 7 nicotinic receptors.

    abstract:AIM:To test whether carbachol can influence endothelial barrier dysfunction induced by tumor necrosis factor (TNF)-α and whether the alpha 7 nicotinic receptor can mediate this process. METHODS:Rat cardiac microvascular endothelial cells were exposed to carbachol followed by TNF-α treatment in the presence or the abse...

    journal_title:Acta pharmacologica Sinica

    pub_type: 杂志文章

    doi:10.1038/aps.2010.165

    authors: Li YZ,Liu XH,Rong F,Hu S,Sheng ZY

    更新日期:2010-10-01 00:00:00

  • Organ preservation: from the past to the future.

    abstract::Organ transplantation is the most effective therapy for patients with end-stage disease. Preservation solutions and techniques are crucial for donor organ quality, which is directly related to morbidity and survival after transplantation. Currently, static cold storage (SCS) is the standard method for organ preservati...

    journal_title:Acta pharmacologica Sinica

    pub_type: 历史文章,杂志文章,评审

    doi:10.1038/aps.2017.182

    authors: Jing L,Yao L,Zhao M,Peng LP,Liu M

    更新日期:2018-05-01 00:00:00

  • Chromosome 1q21 amplification and oncogenes in hepatocellular carcinoma.

    abstract::Hepatocellular carcinoma (HCC) is among the most lethal of human malignancies. During human multistep hepatocarcinogenesis, genomic gain represents an important mechanism in the activation of proto-oncogenes. In many circumstances, activated oncogenes hold clinical implications both as prognostic markers and targets f...

    journal_title:Acta pharmacologica Sinica

    pub_type: 杂志文章,评审

    doi:10.1038/aps.2010.94

    authors: Chen L,Chan TH,Guan XY

    更新日期:2010-09-01 00:00:00

  • Proteome reference map and regulation network of neonatal rat cardiomyocyte.

    abstract:AIM:To study and establish a proteome reference map and regulation network of neonatal rat cardiomyocyte. METHODS:Cultured cardiomyocytes of neonatal rats were used. All proteins expressed in the cardiomyocytes were separated and identified by two-dimensional polyacrylamide gel electrophoresis (2-DE) and matrix-assist...

    journal_title:Acta pharmacologica Sinica

    pub_type: 杂志文章

    doi:10.1038/aps.2011.86

    authors: Li ZJ,Liu N,Han QD,Zhang YY

    更新日期:2011-09-01 00:00:00

  • Association of ALOX15 gene polymorphisms with obesity-related phenotypes in Chinese nuclear families with male offspring.

    abstract:AIM:Genetic variation in ALOX12, which encoded human 12-lipoxygenase, was found to be associated with fat mass in young Chinese men. The objective of this study was to investigate the relationship between single nucleotide polymorphisms (SNPs) and haplotypes in the ALOX15 gene and obesity-related phenotypes in Chinese ...

    journal_title:Acta pharmacologica Sinica

    pub_type: 杂志文章

    doi:10.1038/aps.2011.167

    authors: Ke YH,Xiao WJ,He JW,Zhang H,Yu JB,Hu WW,Gu JM,Gao G,Yue H,Wang C,Hu YQ,Li M,Liu YJ,Fu WZ,Zhang ZL

    更新日期:2012-02-01 00:00:00

  • Protective role of PI3-kinase/Akt/eNOS signaling in mechanical stress through inhibition of p38 mitogen-activated protein kinase in mouse lung.

    abstract:AIM:To test the hypothesis that PI3K/Akt/eNOS signaling has a protective role in a murine model of ventilation associated lung injury (VALI) through down-regulation of p38 MAPK signaling. METHODS:Male C57BL/J6 (wild-type, WT) or eNOS knockout mice (eNOS(-/-)) were exposed to mechanical ventilation (MV) with low (LV(T)...

    journal_title:Acta pharmacologica Sinica

    pub_type: 杂志文章

    doi:10.1038/aps.2009.190

    authors: Peng XQ,Damarla M,Skirball J,Nonas S,Wang XY,Han EJ,Hasan EJ,Cao X,Boueiz A,Damico R,Tuder RM,Sciuto AM,Anderson DR,Garcia JG,Kass DA,Hassoun PM,Zhang JT

    更新日期:2010-02-01 00:00:00

  • Changes and mechanisms of protein-tyrosine kinase and protein-tyrosine phosphatase activities after brain ischemia/reperfusion.

    abstract:AIM:To study the changes and mechanisms of protein-tyrosine kinase (PTK) and protein-tyrosine phosphatase (PTP) activities in the hippocamal synaptosome following cerebral ischemia/reperfusion (I/R) in gerbil. METHODS:Transient (15 min) global ischemia was produced by bilateral carotid artery occlusion. Total PTK and ...

    journal_title:Acta pharmacologica Sinica

    pub_type: 杂志文章

    doi:

    authors: Pei L,Li Y,Yan JZ,Zhang GY,Cui ZC,Zhu ZM

    更新日期:2000-08-01 00:00:00

  • Nimesulide inhibits tumor growth in mice implanted hepatoma: overexpression of Bax over Bcl-2.

    abstract:AIM:To investigate whether nimesulide could suppress tumor growth and induce apoptosis in implanted hepatoma mice and to explore the molecular mechanisms. METHODS:Male mice received nimesulide 10 mg/kg, 20 mg/kg, and 40 mg/kg ig daily for 21 d. Electron microscopy (EM), flow cytometry (FCM), DNA ladder, radioimmunoass...

    journal_title:Acta pharmacologica Sinica

    pub_type: 杂志文章

    doi:

    authors: Li XH,Li JJ,Zhang HW,Sun P,Zhang YL,Cai SH,Ren XD

    更新日期:2003-10-01 00:00:00

  • Bufalin derivative BF211 inhibits proteasome activity in human lung cancer cells in vitro by inhibiting β1 subunit expression and disrupting proteasome assembly.

    abstract:AIM:Bufalin is one of the active components in the traditional Chinese medicine ChanSu that is used to treat arrhythmia, inflammation and cancer. BF211 is a bufalin derivative with stronger cytotoxic activity in cancer cells. The aim of this study was to identify the putative target proteins of BF211 and the signaling ...

    journal_title:Acta pharmacologica Sinica

    pub_type: 杂志文章

    doi:10.1038/aps.2016.30

    authors: Sun P,Feng LX,Zhang DM,Liu M,Liu W,Mi T,Wu WY,Jiang BH,Yang M,Hu LH,Guo DA,Liu X

    更新日期:2016-07-01 00:00:00

  • Therapeutic effects of berberine in impaired glucose tolerance rats and its influence on insulin secretion.

    abstract:AIM:To explore the anti-diabetic effects of berberine and its influence on insulin secretion. METHODS:Impaired glucose tolerance rats induced by iv injection of streptozotocin 30 mg/kg were treated with berberine 187.5 and 562.5 mg/kg while fed with high fat laboratory chow. After rats were treated for 4 weeks, oral g...

    journal_title:Acta pharmacologica Sinica

    pub_type: 杂志文章

    doi:

    authors: Leng SH,Lu FE,Xu LJ

    更新日期:2004-04-01 00:00:00

  • The vascular endothelial growth factor trap aflibercept induces vascular dysfunction and hypertension via attenuation of eNOS/NO signaling in mice.

    abstract::Aflibercept, as a soluble decoy vascular endothelial growth factor receptor, Which has been used as a first-line monotherapy for cancers. Aflibercept often causes cardiovascular toxicities including hypertension, but the mechanisms underlying aflibercept-induced hypertension remain unknown. In this study we investigat...

    journal_title:Acta pharmacologica Sinica

    pub_type: 杂志文章

    doi:10.1038/s41401-020-00569-1

    authors: Dong ZC,Wu MM,Zhang YL,Wang QS,Liang C,Yan X,Zou LX,Chen C,Han X,Zhang B,Zhang ZR

    更新日期:2020-12-10 00:00:00

  • Discrimination analysis of mass spectrometry proteomics for ovarian cancer detection.

    abstract:AIM:A discrimination analysis has been explored for the probabilistic classification of healthy versus ovarian cancer serum samples using proteomics data from mass spectrometry (MS). METHODS:The method employs data normalization, clustering, and a linear discriminant analysis on surface-enhanced laser desorption ioniz...

    journal_title:Acta pharmacologica Sinica

    pub_type: 杂志文章

    doi:10.1111/j.1745-7254.2008.00861.x

    authors: Hong YJ,Wang XD,Shen D,Zeng S

    更新日期:2008-10-01 00:00:00

  • NK3 and NK4 of HGF enhance filamin production via STAT pathway, but not NK1 and NK2 in human breast cancer cells.

    abstract:AIM:The purpose of this study was to reveal the effects of hepatocyte growth factor (HGF) variants on human breast cancer cells and the differential signaling pathways of the variants in controlling cell proliferation and invasion. METHODS:Four HGF variants (NK1, NK2, NK3, and NK4) were created by gene engineering, an...

    journal_title:Acta pharmacologica Sinica

    pub_type: 杂志文章

    doi:10.1111/j.1745-7254.2008.00799.x

    authors: Yin YL,Chen HL,Kuo HM,He SP

    更新日期:2008-06-01 00:00:00

  • Edaravone (MCI-186), a free radical scavenger, attenuates retinal ischemia/reperfusion injury in rats.

    abstract:AIM:To investigate the effect of edaravone (MCI-186), a free radical scavenger, against ischemia/reperfusion (I/R) injury in the rat retina. METHODS:Retinal ischemia was induced in male Sprague-Dawley rats by elevating intraocular pressure to 110 mmHg for 60 min. The rats were intraperitoneally injected with edaravone...

    journal_title:Acta pharmacologica Sinica

    pub_type: 杂志文章

    doi:10.1111/j.1745-7254.2008.00822.x

    authors: Song Y,Gong YY,Xie ZG,Li CH,Gu Q,Wu XW

    更新日期:2008-07-01 00:00:00

  • Rhodanine derivatives as novel peroxisome proliferator-activated receptor gamma agonists.

    abstract:AIM:To characterize the in vitro bioactivities of rhodanine derivatives as novel peroxisome proliferator-activated receptor (PPAR) gamma modulators, based on a hit (SH00012671) identified during high-throughput screening (HTS) of a diverse synthetic compound library, and to preliminarily elucidate the structure-activit...

    journal_title:Acta pharmacologica Sinica

    pub_type: 杂志文章

    doi:

    authors: Liu Q,Zhang YY,Lu HL,Li QY,Zhou CH,Wang MW

    更新日期:2007-12-01 00:00:00