In vivo conversion of gamma-aminobutyric acid and 1,4-butanediol to gamma-hydroxybutyric acid in rat brain. Studies using stable isotopes.

Abstract:

:The formation of 4-[1,4-13C]hydroxybutyric acid ([13C]gamma-hydroxybutyric acid; [13C]GHB) in rat brain was studied following intracerebroventricular (i.c.v.) administration of either 4-[1,4-13C]aminobutyric acid ([13C]GABA or 1,4-[1,4-13C]butanediol ([13C]1,4-BD) to awake, freely moving animals. GHB and [13C]GHB were measured with a gas chromatographic mass spectrometric (GC/MS) technique designed to detect the lactone derivative of GHB with the acid or lactone being determined by conditions of tissue extraction. [13C]GHB was detected following i.c.v. administration of [13C]GABA with a turnover rate of 2.04 nmol/g tissue/hr and [13C]1,4-BD with a turnover rate of 1.4 nmol/g/hr. The formation of [13C]GHB from [13C]GABA was blocked by an inhibitor of GABA-transaminase, but this drug had no effect on the formation of [13C]GHB from [13C]1,4-BD. The latter pathway was also unaffected by alcohol dehydrogenase inhibitors, compounds which block this pathway in the periphery. Further, in the course of these experiments, naturally occurring endogenous gamma-butyrolactone (GBL) was detected in rat brain in a concentration of 200 pmol/g tissue weight, but lactonization in vivo of [13C]GHB formed from either labeled GABA or 1,4-BD was not demonstrated. These data confirm two separate pathways of synthesis for GHB in brain, demonstrate the presence of GBL in brain, and illustrate the utility of a new GC/MS technique for analysis of GHB and for GBL which does not involve extensive derivatization.

journal_name

Biochem Pharmacol

journal_title

Biochemical pharmacology

authors

Snead OC 3rd,Furner R,Liu CC

doi

10.1016/0006-2952(89)90645-x

subject

Has Abstract

pub_date

1989-12-15 00:00:00

pages

4375-80

issue

24

eissn

0006-2952

issn

1873-2968

pii

0006-2952(89)90645-X

journal_volume

38

pub_type

杂志文章
  • Concomitant downregulation of proliferation/survival pathways dependent on FGF-R3, JAK2 and BCMA in human multiple myeloma cells by multi-kinase targeting.

    abstract::The identification of proliferation/survival pathways constitutively activated by genetic alterations in multiple myeloma (MM), or sustained by the bone marrow (BM) microenvironment, provides novel opportunities for the development of targeted therapies. The deregulated function of protein tyrosine kinases plays a cri...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.bcp.2009.06.023

    authors: Cassinelli G,Ronchetti D,Laccabue D,Mattioli M,Cuccuru G,Favini E,Nicolini V,Greco A,Neri A,Zunino F,Lanzi C

    更新日期:2009-11-01 00:00:00

  • Sensitization of human neutrophil defense activities through activation of platelet-activating factor receptors by ginkgolide B, a bioactive component of the Ginkgo biloba extract EGB 761.

    abstract::Ginkgolide B (GKB, BN 52021) was described as a platelet-activating factor (Paf) receptor antagonist. However, it is not known whether all GKB biological effects are mediated through Paf receptor antagonism only. To gain insight into the drug mode of action, we investigated here the effects of GKB per se on functional...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/s0006-2952(01)00866-8

    authors: Lenoir M,Pedruzzi E,Rais S,Drieu K,Perianin A

    更新日期:2002-04-01 00:00:00

  • Regulation of cyclic AMP metabolism in bovine adrenal medullary cells.

    abstract::The capacity of cultured bovine adrenal medullary cells to metabolize and export cyclic AMP has been studied. Basal cellular cyclic AMP levels were increased 50% by 100 microM 3-isobutyl-1-methylxanthine (IBMX) and rolipram, a class IV (cyclic AMP-specific) phosphodiesterase (PDE) inhibitor. They were not affected by ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(92)90335-g

    authors: Marley PD,Thomson KA

    更新日期:1992-12-01 00:00:00

  • Regulation by serine esterase of histamine release from human leukocytes--I. Direct release of histamine by the serine esterase inhibitors diisopropyl fluorophosphate (DFP) and soman (GD).

    abstract::The serine esterase inhibitor diisopropyl fluorophosphate (DFP) had been reported previously to inhibit IgE-dependent histamine release. Recently, it has been demonstrated that lower concentrations of DFP enhance IgE-dependent histamine release and inhibit desensitization. This manuscript describes the abilities of se...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(86)90686-6

    authors: Meier HL,Gross CL,Papirmeister B

    更新日期:1986-12-01 00:00:00

  • Effects of glimepiride and glibenclamide on insulin and glucagon secretion by the perfused rat pancreas.

    abstract::Glimepiride and glibenclamide act apparently in a closely comparable manner upon both insulin and glucagon release. Except for the decreased efficiency of D-glucose in suppressing glucagon release after a prior exposure of the pancreas to the hypoglycemic sulfonylureas, no evidence was obtained to suggest that a posit...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(91)90435-8

    authors: Ledercq-Meyer V,Akkan AG,Marchand J,Malaisse WJ

    更新日期:1991-09-27 00:00:00

  • SPZ1 is critical for chemoresistance and aggressiveness in drug-resistant breast cancer cells.

    abstract::It is believed that chemotherapeutic agents can enhance the malignancy of treated cancer cells in clinical situations, which is a major problem for chemotherapy. However, the underlying molecular mechanisms are still not fully understood. Here, we demonstrated that chemotherapy up-regulates the levels of spermatogenic...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.bcp.2018.07.046

    authors: Liu X,Han X,Wan X,He C,Wang Y,Mao A,Yu F,Zhou T,Feng L,Zhang P,Jin J,Ma X

    更新日期:2018-10-01 00:00:00

  • The in vitro ketone reduction of warfarin and analogues. Substrate stereoselectivity, product stereoselectivity and species differences.

    abstract::The in vitro metabolic ketone reduction of warfarin and its 4'-analogues acenocoumarol (4'-nitrowarfarin) and 4'-chlorowarfarin has been investigated using microsomal and cytosolic fractions of several species. Both subcellular fractions showed ketone reductase activity. The cytosolic fractions, in most species, exhib...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(89)90635-7

    authors: Hermans JJ,Thijssen HH

    更新日期:1989-10-01 00:00:00

  • Resveratrol inhibits BK-induced COX-2 transcription by suppressing acetylation of AP-1 and NF-κB in human rheumatoid arthritis synovial fibroblasts.

    abstract::Bradykinin (BK) induces inflammation in rheumatoid arthritis (RA). Resveratrol is a potent activator of Sirt1 which could modulate inflammation through deacetylating histones of transcription factors. Here, we investigated the mechanisms underlying BK-induced COX-2 expression which is modulated by resveratrol/Sirt1 in...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.bcp.2017.03.003

    authors: Yang CM,Chen YW,Chi PL,Lin CC,Hsiao LD

    更新日期:2017-05-15 00:00:00

  • 2',2'-Difluoro-deoxycytidine (gemcitabine) incorporation into RNA and DNA of tumour cell lines.

    abstract::Gemcitabine (dFdC) is a new cytidine analogue which is active mainly by the incorporation of its triphosphate (dFdCTP) into DNA, leading to cell death. We determined incorporation of dFdC into nucleic acids of two solid tumour cell lines: the murine colon carcinoma cell line Colon 26-10, the human ovarian carcinoma ce...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(93)90566-f

    authors: Ruiz van Haperen VW,Veerman G,Vermorken JB,Peters GJ

    更新日期:1993-08-17 00:00:00

  • The tyrphostin AG1478 inhibits proliferation and induces death of liver tumor cells through EGF receptor-dependent and independent mechanisms.

    abstract::Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related death. Different signaling pathways are de-regulated in this pathogenesis, among them the epidermal growth factor receptor one (EGFR/Erb1). Here we show that blockage of this pathway by the tyrphostin 4-(3-chloroanilino)-6,7-dimethoxyqui...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.bcp.2011.08.011

    authors: Caja L,Sancho P,Bertran E,Ortiz C,Campbell JS,Fausto N,Fabregat I

    更新日期:2011-12-01 00:00:00

  • Effects of perfluorodecanoic acid on hepatic indices of thyroid status in the rat.

    abstract::Perfluorodecanoic acid (PFDA) alters the circulating level of thyroid hormones, but the physiological significance of this change at the target tissue remains to be defined. To this end, the activities of thyroid-responsive hepatic enzymes were examined in adult male rats 1 week after treatment with a single dose of P...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(87)90091-8

    authors: Kelling CK,Van Rafelghem MJ,Menahan LA,Peterson RE

    更新日期:1987-04-15 00:00:00

  • Trifluoromethanesulfonamide anthelmintics. Protonophoric uncouplers of oxidative phosphorylation.

    abstract::A series of trifluoromethanesulfonamides (TFMS) was synthesized and tested for uncoupling activity in rat liver mitochondria. With succinate as the mitochondrial substrate, and the respiratory control index (RCI) as an indicator of their uncoupling ability, we found that all of the TFMS tested were uncouplers of oxida...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(93)90446-4

    authors: McCracken RO,Carr AW,Stillwell WH,Lipkowitz KB,Boisvenue R,O'Doherty GO,Wickiser DI

    更新日期:1993-05-05 00:00:00

  • Immunocytochemical localization of cytochrome P-450 in hepatic and extra-hepatic tissues of the rat with a monoclonal antibody against cytochrome P-450 c.

    abstract::The cellular distribution of cytochrome P-450 has been studied in the liver and a number of extrahepatic tissues in the rat by immunocytochemistry, using an antibody raised against cytochrome P-450 form c. Immunoreactive cytochrome P-450, most probably form c, was found in the proximal tubules of the kidney, in the Cl...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(86)90777-x

    authors: Foster JR,Elcombe CR,Boobis AR,Davies DS,Sesardic D,McQuade J,Robson RT,Hayward C,Lock EA

    更新日期:1986-12-15 00:00:00

  • The stimulatory effects of cationic amphiphilic drugs on human platelets treated with thrombin.

    abstract::The actions of eight cationic amphiphilic drugs on human platelets displayed three different effects according to drug concentration ranges. At lower concentrations (below approximately 25 microM), the drugs stimulated secretory responses induced by 0.2 U/mL of thrombin, while at concentrations in the 25-50 microM ran...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/s0006-2952(00)00445-7

    authors: Tharmapathy P,Fukami MH,Holmsen H

    更新日期:2000-11-01 00:00:00

  • Azalanstat (RS-21607), a lanosterol 14 alpha-demethylase inhibitor with cholesterol-lowering activity.

    abstract::Agents that inhibit hepatic cholesterol biosynthesis reduce circulating cholesterol levels in experimental animals and humans, and may be of pharmacological importance in the prevention of atherosclerosis. Azalanstat (RS-21607), a synthetic imidazole, has been shown to inhibit cholesterol synthesis in HepG2 cells, hum...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(95)00152-p

    authors: Burton PM,Swinney DC,Heller R,Dunlap B,Chiou M,Malonzo E,Haller J,Walker KA,Salari A,Murakami S

    更新日期:1995-08-08 00:00:00

  • Relationship of biochemical drug effects to their antitumor activity--II. Diacridines and membrane-related reactions.

    abstract::A method is presented that determines the degree of attachment of cancer cells to normal cells. This method may be useful in determining the extent to which treatment of normal cells (or of a tumor-bearing host) with a particular chemotherapeutic agent may affect the degree of attachment of cancer cells to the normal ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(85)90405-8

    authors: Elliott RE,Karadsheh NS,Kole J,Canellakis ES

    更新日期:1985-06-15 00:00:00

  • Chicken DT40 cells stably transfected with the rat P2X7 receptor ion channel: a system suitable for the study of purine receptor-mediated cell death.

    abstract::We have generated and characterised a clone of chicken DT40 lymphocytes stably transfected with the rat P2X(7) receptor (rP2X(7)). Successful transfection was confirmed by Western blotting. Under voltage clamp, P2X(7)-expressing cells responded to ATP and dibenzoyl-ATP (Bz-ATP) (a more potent P2X(7) receptor agonist) ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/s0006-2952(03)00286-7

    authors: Hillman KA,Harada H,Chan CM,Townsend-Nicholson A,Moss SE,Miyamoto K,Suketa Y,Burnstock G,Unwin RJ,Dunn PM

    更新日期:2003-08-01 00:00:00

  • Intestinal cell-specific vitamin D receptor (VDR)-mediated transcriptional regulation of CYP3A4 gene.

    abstract::CYP3A4 is the most important drug-metabolizing enzyme that is involved in biotransformation of more than 50% of drugs. Pregnane X receptor (PXR) dominantly controls CYP3A4 inducibility in the liver, whereas vitamin D receptor (VDR) transactivates CYP3A4 in the intestine by secondary bile acids. Four major functional P...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.bcp.2009.08.017

    authors: Pavek P,Pospechova K,Svecova L,Syrova Z,Stejskalova L,Blazkova J,Dvorak Z,Blahos J

    更新日期:2010-01-15 00:00:00

  • Reactive oxygen intermediates as mediators of programmed cell death in plants and animals.

    abstract::Programmed cell death (PCD) is a physiological process occurring during development and in pathological conditions of animals and plants. The cell death program can be subdivided into three functionally different phases: a stimulus-dependent induction phase, an effector phase during which the wide range of death-stimu...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章,评审

    doi:10.1016/s0006-2952(98)00227-5

    authors: Jabs T

    更新日期:1999-02-01 00:00:00

  • In vitro and in vivo inhibition by benserazide of clorgyline-resistant amine oxidases in rat cardiovascular tissues.

    abstract::Bernserazide (D,L-serine 2-[2,3,4-trihydroxybenzyl]-hydrazide) as been shown to inhibit the clorgyline-resistant amine oxidase (CRAO) activities which metabolize benzylamine in homogenates of rat aorta, heart and brown adipose tissue. In vitro studies showed a concentration- and time-dependent inhibition of CRAO in he...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(82)90037-5

    authors: Lyles GA,Callingham BA

    更新日期:1982-04-01 00:00:00

  • Growth factors, cytokines and their receptors as downstream targets of arylhydrocarbon receptor (AhR) signaling pathways.

    abstract::2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a widespread environmental pollutant, which causes a variety of severe health effects, e.g. immunosuppression, hepatotoxicity, and carcinogenesis. The main mediator of TCDD toxicity is the arylhydrocarbon receptor (AhR), which, upon activation, translocates into the nucleu...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章,评审

    doi:10.1016/j.bcp.2008.09.013

    authors: Haarmann-Stemmann T,Bothe H,Abel J

    更新日期:2009-02-15 00:00:00

  • Actions of epoxyeicosatrienoic acid on large-conductance Ca(2+)-activated K(+) channels in pituitary GH(3) cells.

    abstract::Epoxyeicosatrienoic acids (EETs), a family of cytochrome P450 epoxygenase metabolites of arachidonic acid, are believed to have an autocrine or paracrine role in the regulation of neurons or neuroendocrine cells. The effects of 14,15-EET on ionic currents were investigated in rat pituitary GH(3) cells. In the whole-ce...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/s0006-2952(00)00317-8

    authors: Wu SN,Li HF,Chiang HT

    更新日期:2000-07-15 00:00:00

  • Diclofenac induces apoptosis in hepatocytes by alteration of mitochondrial function and generation of ROS.

    abstract::Diclofenac is a non-steroidal anti-inflammatory drug that is widely used clinically but side effects associated with the administration of the drug have been reported. The apoptotic effect of the drug has been evaluated in human and rat hepatocytes. Apoptosis was observed after exposure to sub-cytotoxic concentrations...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.bcp.2003.08.003

    authors: Gómez-Lechón MJ,Ponsoda X,O'Connor E,Donato T,Castell JV,Jover R

    更新日期:2003-12-01 00:00:00

  • Identification of new shikonin derivatives as STAT3 inhibitors.

    abstract::The signal transducer and activator of transcription 3 is a constitutively activated oncogenic protein in various human tumors and represents a valid target for anticancer drug design. In this study, we have achieved a new type of STAT3 inhibitors based on structural modifications on shikonin scaffold, guided by compu...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.bcp.2017.10.009

    authors: Qiu HY,Fu JY,Yang MK,Han HW,Wang PF,Zhang YH,Lin HY,Tang CY,Qi JL,Yang RW,Wang XM,Zhu HL,Yang YH

    更新日期:2017-12-15 00:00:00

  • Cisplatin-induced apoptosis by translocation of endogenous Bax in mouse collecting duct cells.

    abstract::cis-platinum(II) (cis-diammine dichloroplatinum; cisplatin) is a potent antitumor compound that is widely used for the treatment of many malignancies. An important side-effect of cisplatin is nephrotoxicity, which results from injury to renal tubular epithelial cells and can be manifested as either acute renal failure...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/s0006-2952(01)00748-1

    authors: Lee RH,Song JM,Park MY,Kang SK,Kim YK,Jung JS

    更新日期:2001-10-15 00:00:00

  • Differences in the biochemical properties of aldrin epoxidase, a cytochrome P-450-dependent monooxygenase, in various tissues.

    abstract::Aldrin epoxidase, a cytochrome P-450-dependent monooxygenase, was studied in the lung and kidney of male rats. The sensitivity of the liver enzyme activity to different chemicals in vitro was influenced by the treatment of the animals with phenobarbital or methylcholanthrene. These results confirm that more than one f...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(83)90078-3

    authors: Van Cantfort J,Léonard-Poma M,Sèle-Doyen J,Gielen JE

    更新日期:1983-09-15 00:00:00

  • Inhibition of purine catabolism by benzbromarone in isolated rat liver cells. Comparison with allopurinol and probenecid.

    abstract::Benzbromarone, a potent uricosuric agent, inhibited allantoin production in isolated hepatocytes at concentrations half to ten times greater than therapeutic plasma levels of the drug. In addition, the drug at these concentrations also markedly inhibited xanthine oxidase (EC 1.2.1.37), an enzyme involved in the regula...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(88)90385-1

    authors: Rodilla F,Sanchez-Beltran MJ,Izquierdo R,Gomez-Ruiz MD,Cabo J

    更新日期:1988-10-01 00:00:00

  • Sulfur amino acid metabolism in Zucker diabetic fatty rats.

    abstract::The present study was aimed to investigate the metabolomics of sulfur amino acids in Zucker diabetic fatty (ZDF) rats, an obese type 2 diabetic animal model. Plasma levels of total cysteine, homocysteine and methionine, but not glutathione (GSH) were markedly decreased in ZDF rats. Hepatic methionine, homocysteine, cy...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.bcp.2015.05.014

    authors: Kwak HC,Kim YM,Oh SJ,Kim SK

    更新日期:2015-08-01 00:00:00

  • Site-specific DNA cleavage by Cu(II) complexes of podophyllotoxin derivatives.

    abstract::Site-specific DNA cleavage in the presence of Cu(II) complexes of podophyllotoxin derivatives was investigated with a modified Sanger sequencing method. Cu(II) complexes of 4'-demethylepipodophyllotoxin (DEPD) and syringic acid (SA) cleaved M13mp18 single-strand DNA site-specifically at both cytosine (C) and guanine (...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(94)90324-7

    authors: Yamashita A,Tawa R,Imakura Y,Lee KH,Sakurai H

    更新日期:1994-05-18 00:00:00

  • Effect of manganese on tyrosylprotein sulfotransferase activity in PC12 cells.

    abstract::Recent studies in our laboratory have revealed that Mn2+ is capable of promoting cell spreading and neurite outgrowth in PC12 cells, a process which is dependent on Mn2+ stimulation of the interaction between extracellular matrix (ECM) components and their corresponding integrin receptors. Since the major ECM proteins...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(94)90534-7

    authors: Lin WH,Marcucci K,Roth JA

    更新日期:1994-04-29 00:00:00