当前位置： SCI文献检索 > LIFE SCIENCES期刊下所有文献 > Brain distribution of 6-mercaptopurine is regulated by the efflux transport system in the blood-brain barrier.

Brain distribution of 6-mercaptopurine is regulated by the efflux transport system in the blood-brain barrier.

Abstract：

:6-mercaptopurine (6-MP) has been used clinically for 40 years to maintain remission in patients with acute lymphoblastic leukemia (ALL). However, central nervous system (CNS) relapses frequently occur in patients with ALL who continuously receive anticancer drugs, including 6-MP, during remission maintenance therapy. The cause of such CNS relapse is not well understood. One possible reason may involve the restricted distribution of 6-MP in the brain. This study, therefore, investigates the blood-brain barrier (BBB) transport which largely regulates 6-MP distribution in the brain using a quantitative microdialysis technique and centers on the efflux transport of 6-MP across the BBB. The brain tissue, cerebrospinal fluid (CSF), or hippocampal interstitial fluid (ISF) concentration of 6-MP was very low compared with the unbound plasma concentration, suggesting that 6-MP distribution in the brain is highly restricted. Kinetic analyses of this BBB transport showed that the efflux clearance from brain ISF to plasma across the BBB (CLout) is approximately 20-times greater than the influx clearance from plasma to brain (CLin). The CLout was significantly reduced by 1mM N-ethylmaleimide (NEM), a sulfhydryl-modifying agent, suggesting the participation of transport protein in the efflux of 6-MP across the BBB. In addition, efflux transport was inhibited by an intracerebral infusion of probenecid (1.5 mM), p-aminohippuric acid (PAH, 3.0 mM), benzoate (3.6 mM), or salicylate (3.7 mM) administered through a microdialysis probe, but neither choline (0.8 mM) nor tetraethylammonium (TEA, 0.7 mM) had any effect. These data suggest that the restricted 6-MP brain distribution may be ascribed to efficient efflux from the brain, possibly via both the organic anion transport system, shared with probenecid and PAH, and the monocarboxylic acid transport system, shared with benzoate and salicylate.

journal_name

Life Sci

journal_title

Life sciences

authors

Deguchi Y,Yokoyama Y,Sakamoto T,Hayashi H,Naito T,Yamada S,Kimura R

doi

10.1016/s0024-3205(99)00637-2

subject

Has Abstract

pub_date

2000-01-01 00:00:00

pages

649-62

issue

7

eissn

0024-3205

issn

1879-0631

pii

S0024320599006372

journal_volume

66

pub_type

杂志文章

相关文献

LIFE SCIENCES文献大全
  • 17-DMAG, an Hsp90 inhibitor, ameliorates ovariectomy-induced obesity in rats.

    abstract：AIMS:Obesity is not only associated with metabolic diseases but is also a symptom of menopause in women. To date, there are no effective drugs for the management of obesity, and it is important to find new agents with fewer side effects, for the treatment of obesity. This study aimed to determine the anti-obesity effec...

    journal_title：Life sciences

    pub_type： 杂志文章

    doi：10.1016/j.lfs.2019.116672

    authors： Tsai YC,Leu SY,Chen SY,Kung CW,Lee YM,Liu YP,Yen MH,Cheng PY

    更新日期：2019-09-01 00:00:00

  • Inhibition of adenylate cyclase activity by polyamines in human erythrocyte plasma membranes.

    abstract：:Polyamines (spermidine, spermine and putrescine) inhibited the adenylate cyclase activity in a concentration dependent manner in human erythrocyte plasma membranes. Spermidine (Spd) exhibited more inhibitory effect than spermine (Spm) and putrescine (Put). On the contrary, the addition of amino acids (arginine, glutam...

    journal_title：Life sciences

    pub_type： 杂志文章

    doi：10.1016/0024-3205(90)90055-v

    authors： Khan NA,Quemener V,Moulinoux P

    更新日期：1990-01-01 00:00:00

  • The MIR155 host gene/microRNA-627/HMGB1/NF-κB loop modulates fibroblast proliferation and extracellular matrix deposition.

    abstract：:Pulmonary fibrosis (PF), which is characterized by excessive matrix formation, may ultimately lead to irreversible lung damage and thus death. Fibroblast activation has been regarded as a central event during PF pathogenesis. In our previous study, we confirmed that the miR-627/high-mobility group box protein 1 (HMGB1...

    journal_title：Life sciences

    pub_type： 杂志文章

    doi：10.1016/j.lfs.2021.119085

    authors： Li J,Zhang X,Wang T,Li J,Su Q,Zhong C,Chen Z,Liang Y

    更新日期：2021-01-20 00:00:00

  • MMP-9 antisense oligodeoxynucleotide exerts an inhibitory effect on osteoclastic bone resorption by suppressing cell migration.

    abstract：:We have previously shown that matrix metalloproteinases (MMPs) play a role in osteoclastic bone resorption by facilitating migration of osteoclastic cells toward bone surface through matrices. Of MMPs identified so far, MMP-9 is likely the most important proteinase for the action, since osteoclasts express this enzyme...

    journal_title：Life sciences

    pub_type： 杂志文章

    doi：10.1016/j.lfs.2006.05.024

    authors： Ishibashi O,Niwa S,Kadoyama K,Inui T

    更新日期：2006-09-20 00:00:00

  • Synaptobrevin isoforms in secretory granules and synaptic-like microvesicles in anterior pituitary cells.

    abstract：:A set of synaptic proteins have been shown to be essential for the life cycle and exocytosis of synaptic vesicles at the nerve terminal. Recently, these proteins have also been identified in certain endocrine cells. Here we analysed the presence and location of some of these synaptic proteins in anterior pituitary cel...

    journal_title：Life sciences

    pub_type： 杂志文章

    doi：10.1016/s0024-3205(97)01156-9

    authors： Majó G,Aguado F,Blasi J,Marsal J

    更新日期：1998-01-01 00:00:00

  • Behavioral pharmacology of designer cathinones: a review of the preclinical literature.

    abstract：:"Bath salts" is one street name for a family of synthetic cathinones that display pharmacological effects resembling cocaine and commonly abused amphetamines. Despite extensive legislation aimed at the criminalization of bath salts, several designer cathinones are gaining a foothold in the illicit drug scene; for exam...

    journal_title：Life sciences

    pub_type： 杂志文章,评审

    doi：10.1016/j.lfs.2013.10.033

    authors： Gregg RA,Rawls SM

    更新日期：2014-02-27 00:00:00

  • VIP-ellipticine derivatives inhibit the growth of breast cancer cells.

    abstract：:The effects of vasoactive intestinal peptide (VIP)-ellipticine (E) derivatives were investigated on breast cancer cells. VIP-ALALA-E and VIP-LALA-E inhibited 125I-VIP binding to MCF-7 cells with an IC(50) values of 1 and 0.2 microM respectively. VIP-ALALA-E and VIP-LALA-E caused elevation of cAMP in MCF-7 cells with E...

    journal_title：Life sciences

    pub_type： 杂志文章

    doi：10.1016/s0024-3205(02)01741-1

    authors： Moody TW,Czerwinski G,Tarasova NI,Michejda CJ

    更新日期：2002-07-19 00:00:00

  • Stereospecific effects of d- and l-pentazocine on contractions of the mouse vas deferens.

    abstract：:The effects of the d- and l-isomers of pentazocine were compared to that of racemic pentazocine on contractions of the mouse isolated vas deferens. L-pentazocine inhibited electrically evoked contractions of the mouse vas deferens (MVD) in a dose-dependent manner (ID50 0.37 +/- 0.04 microM). In contrast, d-pentazocine...

    journal_title：Life sciences

    pub_type： 杂志文章

    doi：10.1016/0024-3205(86)90446-7

    authors： Kinouchi K,Fukumitsu K,Takezawa J,Maeda S,Enomoto H,Kakuhari J,Yoshiya I,Inoki R

    更新日期：1986-07-14 00:00:00

  • Radioprotective efficacy of delta-tocotrienol, a vitamin E isoform, is mediated through granulocyte colony-stimulating factor.

    abstract：AIMS:The objectives of this study were to determine the cytokine induction by delta tocotrienol (DT3, a promising radiation countermeasure) and to investigate the role of granulocyte colony-stimulating factor (G-CSF) in its radioprotective efficacy against ionizing radiation in mice. MAIN METHODS:Multiplex Luminex was...

    journal_title：Life sciences

    pub_type： 杂志文章

    doi：10.1016/j.lfs.2014.01.065

    authors： Singh VK,Wise SY,Scott JR,Romaine PL,Newman VL,Fatanmi OO

    更新日期：2014-03-11 00:00:00

  • Extracellular superoxide dismutase ameliorates streptozotocin-induced rat diabetic nephropathy via inhibiting the ROS/ERK1/2 signaling.

    abstract：AIM:Diabetic nephropathy is the leading cause of end stage renal disease in developed countries throughout the world. The imbalance between the production of reactive oxygen species (ROS) and the antioxidant defense system is the main problem that is responsible for the progression of diabetic kidney disease. In this s...

    journal_title：Life sciences

    pub_type： 杂志文章

    doi：10.1016/j.lfs.2015.04.018

    authors： Kuo CW,Shen CJ,Tung YT,Chen HL,Chen YH,Chang WH,Cheng KC,Yang SH,Chen CM

    更新日期：2015-08-15 00:00:00

  • Low levels of eicosapentaenoic and docosahexaenoic acids mimic the effects of fish oil upon rat lymphocytes.

    abstract：:Fish oil is rich in the long chain n-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA); typically these fatty acids constitute 20 to 25 g/100 g total fatty acids in fish oil. Feeding rodents diets rich in fish oil has been shown to decrease lymphocyte proliferation and natural ki...

    journal_title：Life sciences

    pub_type： 杂志文章

    doi：10.1016/s0024-3205(98)00199-4

    authors： Peterson LD,Thies F,Sanderson P,Newsholme EA,Calder PC

    更新日期：1998-01-01 00:00:00

  • Critical role of neutrophil alkaline phosphatase in the antimicrobial function of neutrophils.

    abstract：AIMS:To investigate the roles of neutrophil alkaline phosphatase (NAP) in the migration, reactive oxygen species (ROS) generation and apoptosis of neutrophils. MAIN METHODS:NAP was overexpressed in neutrophil-like differentiated HL-60 cells via transfecting coding sequence of NAP by lentivirus. NAP overexpression in H...

    journal_title：Life sciences

    pub_type： 杂志文章

    doi：10.1016/j.lfs.2016.06.005

    authors： Li H,Zhao Y,Li W,Yang J,Wu H

    更新日期：2016-07-15 00:00:00

  • Thalidomide derivatives and the immune system. 6. Effects of two derivatives with no obvious teratogenic potency on the pattern of integrins and other surface receptors on blood cells of marmosets.

    abstract：:The two thalidomide (Thd) derivatives beta-EM12 and phthalimidophthalimide (Phtpht), which exhibit no obvious teratogenicity, were tested for their ability to induce changes in the pattern of lymphocyte subpopulations, and especially changes in integrin receptors, in marmosets (Callithrix jacchus). Previously, Thd and...

    journal_title：Life sciences

    pub_type： 杂志文章

    doi：10.1016/0024-3205(95)02293-7

    authors： Nogueira AC,Neubert R,Felies A,Jacob-Müller U,Frankus E,Neubert D

    更新日期：1996-01-01 00:00:00

  • Stimulation of muscarinic cholinoceptive neurons in the hippocampus evokes a pressor response with bradycardia.

    abstract：:The injection of neostigmine into the hippocampus of anesthetized rats increased the mean arterial blood pressure (17% of baseline after 60 min injection) and decreased the heart rate (24% of baseline after 60 min injection). These changes were blocked by the co-administration of methylatropine into the hippocampus. I...

    journal_title：Life sciences

    pub_type： 杂志文章

    doi：10.1016/0024-3205(92)90377-2

    authors： Haruta K,Iguchi A,Matsubara T,Itoh K,Chen CL,Yoshida S,Terada R,Kanashiro M,Suzuki O,Nishimura H

    更新日期：1992-01-01 00:00:00

  • Apoptosis and autophagy contribute to gender difference in cardiac ischemia-reperfusion induced injury in rats.

    abstract：AIMS:Gender difference in cardiac ischemia-reperfusion (IR) induced injury has been reported in animal models. However, a large-scale clinical trial found an increase in cardiovascular incidents in women with hormone replacement therapy. The present study is aimed to explore possible mechanisms of gender difference in ...

    journal_title：Life sciences

    pub_type： 杂志文章

    doi：10.1016/j.lfs.2013.06.019

    authors： Chen C,Hu LX,Dong T,Wang GQ,Wang LH,Zhou XP,Jiang Y,Murao K,Lu SQ,Chen JW,Zhang GX

    更新日期：2013-08-28 00:00:00

  • Aerobic exercise attenuates ectopic renal sinus adipose tissue accumulation-related renal hypoxia injury in obese mice.

    abstract：AIMS:We explored the effect of aerobic exercise on renal sinus adipose (RSA) accumulation and RSA accumulation-related renal injury in obese mice. MAIN METHODS:C57BL/6J male mice (n = 30) were evenly divided into three groups: control group (CON, n = 10), obese group (OB, n = 10; given high-fat diet) and obese + aerob...

    journal_title：Life sciences

    pub_type： 杂志文章

    doi：10.1016/j.lfs.2021.119106

    authors： Wang SS,Gu Q,Liu N,Li J,Liu X

    更新日期：2021-01-23 00:00:00

  • BRCA1 protects cardiac microvascular endothelial cells against irradiation by regulating p21-mediated cell cycle arrest.

    abstract：AIMS:Microvascular endothelial cell dysfunction is a leading cause of radiation-induced heart disease (RIHD). BRCA1 plays an important role in DNA damage repair. The study aims to explore the effect of BRCA1 in endothelial cells involved in RIHD. MATERIALS AND METHODS:BRCA1 and p21 expression were detected in human um...

    journal_title：Life sciences

    pub_type： 杂志文章

    doi：10.1016/j.lfs.2020.117342

    authors： Zeng ZM,Du HY,Xiong L,Zeng XL,Zhang P,Cai J,Huang L,Liu AW

    更新日期：2020-03-01 00:00:00

  • Mucocutaneous cholinergic system is targeted in mustard-induced vesication.

    abstract：:The purpose of this research is to elucidate the pharmacological mechanism mediating vesicating effects of sulfur mustard (HD) and identify an antidote to its action. HD causes blisters because epithelial cells lose their attachments. Epithelial cell adhesion is under control of the local cytotransmitter acetylcholine...

    journal_title：Life sciences

    pub_type： 杂志文章

    doi：10.1016/s0024-3205(03)00074-2

    authors： Grando SA

    更新日期：2003-03-28 00:00:00

  • Chronic intermittent hypoxia stimulates testosterone production in rat Leydig cells.

    abstract：AIMS:The hypoxia-stimulated response of the endocrine system depends on the kind and duration of hypoxia. Hypoxia has been reported to stimulate testosterone (T) production in rats, but the mechanisms remain to be investigated. MATERIALS AND METHODS:Male rats were divided into two groups. The rats exposed to chronic i...

    journal_title：Life sciences

    pub_type： 杂志文章

    doi：10.1016/j.lfs.2019.116694

    authors： Cho YM,Chou JC,Fang CM,Hu S,Wang KL,Wang SW,Wang PS

    更新日期：2019-09-15 00:00:00

  • Uncoupling of receptors is essential for opiate-induced desensitization (tolerance) in neuroblastoma x glioma hybrid cells NG 108-15.

    abstract：:Neuroblastoma x glioma hybrid cells NG 108-15 were chronically treated with opioid agonists and tested for their development of "tolerance" as evaluated by the loss of inhibitory activity of opioids upon cAMP-accumulation. Desensitization was dose-dependent and non-competitive and highly selective, since the activity ...

    journal_title：Life sciences

    pub_type： 杂志文章

    doi：10.1016/0024-3205(83)90512-x

    authors： Wüster M,Costa T,Gramsch C

    更新日期：1983-01-01 00:00:00

  • Knockdown of circ_0084043 suppresses the development of human melanoma cells through miR-429/tribbles homolog 2 axis and Wnt/β-catenin pathway.

    abstract：AIMS:Circular RNAs (circRNAs) have been emerged as novel regulators in multiple tumorigenesis, including melanoma. CircRNA_0084043 was recently demonstrated to be deregulated in human melanoma cells. Nevertheless, its role and mechanism are largely unrevealed in melanoma. MATERIALS AND METHODS:Expression of circ_00840...

    journal_title：Life sciences

    pub_type： 杂志文章

    doi：10.1016/j.lfs.2020.117323

    authors： Chen Z,Chen J,Wa Q,He M,Wang X,Zhou J,Cen Y

    更新日期：2020-02-15 00:00:00

  • The aging brain: protein phosphorylation as a target of changes in neuronal function.

    abstract：:There is evidence that senescence affects neurotransmission at different levels. In particular, this review summarizes the studies on age-dependent modifications in protein phosphorylation, which represents the final pathway in the action of transmitters and hormones at neuronal level. Cyclic AMP-dependent protein kin...

    journal_title：Life sciences

    pub_type： 杂志文章,评审

    doi：10.1016/0024-3205(91)90492-t

    authors： Magnoni MS,Govoni S,Battaini F,Trabucchi M

    更新日期：1991-01-01 00:00:00

  • Characterization of monoamine oxidase isoforms in human islets of Langerhans.

    abstract：:In this paper, we describe the characterization of the expression of monoamine oxidase (MAO) in whole pancreas and in isolated islets of Langerhans from human. Classical monamine oxidase activity assays reveal that both isoforms A & B are present in human pancreas. Two complementary approaches indicated that both MAO ...

    journal_title：Life sciences

    pub_type： 杂志文章

    doi：10.1016/s0024-3205(99)00265-9

    authors： Pizzinat N,Chan SL,Remaury A,Morgan NG,Parini A

    更新日期：1999-01-01 00:00:00

  • The level of effort, rather than muscle exercise intensity determines strength gain following a six-week training.

    abstract：AIM:This study investigated the effect of voluntary motor effort during a low-intensity (30% maximal voluntary contraction [MVC]) muscle exercise training program on increasing muscle strength. MATERIALS AND METHODS:Eighteen young and healthy individuals were randomly assigned to one of three groups: high mental effor...

    journal_title：Life sciences

    pub_type： 杂志文章,随机对照试验

    doi：10.1016/j.lfs.2017.04.003

    authors： Jiang CH,Ranganathan VK,Siemionow V,Yue GH

    更新日期：2017-06-01 00:00:00

  • Zoledronic acid inhibits thyroid cancer stemness and metastasis by repressing M2-like tumor-associated macrophages induced Wnt/β-catenin pathway.

    abstract：AIMS:This study aims to explore the effect and underlying mechanism of zoledronic acid (ZA) on the incidence of thyroid cancer (TC) tumorigenesis. MATERIALS AND METHODS:Human mononuclear cells THP-1 were differentiated into M2-like tumor associated macrophages (TAMs) by incubation with PMA followed by additional incub...

    journal_title：Life sciences

    pub_type： 杂志文章

    doi：10.1016/j.lfs.2020.117925

    authors： Lv J,Chen FK,Liu C,Liu PJ,Feng ZP,Jia L,Yang ZX,Hou F,Deng ZY

    更新日期：2020-09-01 00:00:00

  • Benidipine, an anti-hypertensive drug, relaxes mouse airway smooth muscle.

    abstract：AIMS:Benidipine is a dihydropyridine (DHP) derived Ca2+ antagonist, can block triple Ca2+ channels (L, N, and T). It has been used as a safety anti-hypertensive drug because of its long-acting relaxant effect on vascular smooth muscle (VSM). However, whether benidipine has similar pharmacological actions in airway smoo...

    journal_title：Life sciences

    pub_type： 杂志文章

    doi：10.1016/j.lfs.2019.04.036

    authors： Yang Y,Chen W,Wen N,Cai C,Liu QH,Shen J

    更新日期：2019-06-15 00:00:00

  • LncRNA TUG1 regulates proliferation and apoptosis by regulating miR-148b/IGF2 axis in ox-LDL-stimulated VSMC and HUVEC.

    abstract：:Vascular smooth muscle cell (VSMC) accumulation and endothelial cell dysfunction are associated with pathogenesis of atherosclerosis. Long noncoding RNA taurine up-regulated gene 1 (TUG1) has been reported to play an important role in cardiovascular diseases, including atherosclerosis. However, the regulatory mechanis...

    journal_title：Life sciences

    pub_type： 杂志文章

    doi：10.1016/j.lfs.2020.117287

    authors： Wu X,Zheng X,Cheng J,Zhang K,Ma C

    更新日期：2020-02-15 00:00:00

  • In vivo therapy of myocardial infarction with mesenchymal stem cells modified with prostaglandin I synthase gene improves cardiac performance in mice.

    abstract：AIM:Intra-myocardial injection of adult bone marrow-derived stem cells (MSC) has recently been proposed as a therapy to repair damaged cardiomyocytes after acute myocardial infarction (AMI). PGI(2) has vasodilatation effects; however, the effects of combining both MSC and PGI(2) therapy on AMI have never been evaluated...

    journal_title：Life sciences

    pub_type： 杂志文章

    doi：10.1016/j.lfs.2010.12.020

    authors： Lian WS,Cheng WT,Cheng CC,Hsiao FS,Chen JJ,Cheng CF,Wu SC

    更新日期：2011-02-28 00:00:00

  • Synergistic effects of adipose-derived stem cells combined with decellularized myocardial matrix on the treatment of myocardial infarction in rats.

    abstract：AIMS:The aims of the study are to investigate whether the combination of adipose-derived stem cells (ADSCs) with decellularized extracellular matrix (dECM) of myocardium can exert synergistic therapeutic effects on acute MI and the underlying mechanism. MAIN METHODS:Myocardial dECM from fresh porcine myocardium was pr...

    journal_title：Life sciences

    pub_type： 杂志文章

    doi：10.1016/j.lfs.2019.116891

    authors： Qiao L,Kong Y,Shi Y,Sun A,Ji R,Huang C,Li Y,Yang X

    更新日期：2019-12-15 00:00:00

  • Inhibition by angiotensin converting enzyme inhibitors of endothelin secretion from cultured human endothelial cells.

    abstract：:We conducted a study to determine whether angiotensin converting enzyme inhibitors (ACEIs) inhibit endothelin secretion from cultured human endothelial cells. Confluent umbilical vein endothelial cells were incubated in multi-well plates with culture medium containing either captopril (10(-6), 10(-5), 10(-4) M) or ena...

    journal_title：Life sciences

    pub_type： 杂志文章

    doi：10.1016/0024-3205(92)90432-o

    authors： Yoshida H,Nakamura M

    更新日期：1992-01-01 00:00:00