Arachidonic acid metabolism in cultured aortic endothelial cells. Effect of cAMP and 3-isobutyl-1-methylxanthine.


:To investigate the hypothesis that cyclic AMP (cAMP) regulates arachidonic acid metabolism in vascular tissue, we have studied the effects of forskolin (FSK), an activator of adenylate cyclase, and 3-isobutyl-1-methylxanthine (IBMX), a phosphodiesterase inhibitor, on hormone-stimulated prostacyclin (PGI2) synthesis in porcine aortic endothelial cells grown in culture. In these experiments, bradykinin (1 microgram/ml) and A23187 (0.2 microM) potently stimulated PGI2 biosynthesis (9- and 10-fold respectively). However, prostaglandin synthesis in response to either of these agents was not affected by FSK even though FSK elevated intracellular levels of cAMP 10-fold. IBMX failed to elevate basal cAMP levels when incubated with unstimulated cells. Stimulation of IBMX-treated (0.1 but not 1.0 or 4.0 mM) cells with bradykinin, however, did result in increased cAMP levels, presumably due to PGI2 formation and subsequent activation of adenylate cyclase. In addition to phosphodiesterase inhibition, IBMX inhibited PGI2 formation (72% at 1 mM) in a dose-dependent manner so that, at higher doses of IBMX, cAMP levels returned to baseline. Thus, prostacyclin synthesis inhibition by IBMX could not be attributed to elevated cAMP. In other experiments, IBMX (1 mM) was found to directly inhibit arachidonic acid release (32%) and arachidonic acid metabolism (65%) in endothelial cells and to inhibit arachidonic acid conversion to PGE2 by sheep seminal vesicle microsomes (65%). These data suggest that IBMX directly inhibits both phospholipase and cyclooxygenase activities. These experiments do not support the contention that cAMP regulates these enzymes in cultured aortic endothelial cells.


Biochem Pharmacol


Biochemical pharmacology


Whorton AR,Collawn JB,Montgomery ME,Young SL,Kent RS




Has Abstract


1985-01-01 00:00:00














  • Similar pyruvate kinase modifications in glioblastoma cells by 7β-hydroxycholesterol and glutamine withdrawal.

    abstract::Oxysterols possess anti-proliferative properties that may be used with much effect in the treatment of cancer. We have demonstrated previously that 7 beta-hydroxycholesterol (7b-HC) provokes both metabolic stress, as witnessed by AMPK activation, and changes in lipid raft composition in C6 glioblastoma cells. These ob...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: de Weille J,Fabre C,Gaven C,Bakalara N

    更新日期:2013-07-01 00:00:00

  • Tenofovir alafenamide (TAF) as the successor of tenofovir disoproxil fumarate (TDF).

    abstract::Tenofovir alafenamide (TAF) can be considered a new prodrug of tenofovir (TFV), as successor of tenofovir disoproxil fumarate (TDF). It is in vivo as potent against human immunodeficiency virus (HIV) at a 30-fold lower dose (10mg) than TDF (300mg). TAF has been approved in November 2015 (in the US and EU), as a single...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章,评审


    authors: De Clercq E

    更新日期:2016-11-01 00:00:00

  • Protective effect of interleukin-6 against the death of PC12 cells caused by serum deprivation or by the addition of a calcium ionophore.

    abstract::Interleukin-6 (IL-6) is known to differentiate the rat pheochromocytoma cell line PC12 to neuron-like cells. We examined the effect of IL-6 on the death of PC12 cells. IL-6 significantly blocked the death of PC12 cells by serum deprivation. The protective effect of IL-6 was increased by preincubation of PC12 with IL-6...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Umegaki H,Yamada K,Naito M,Kameyama T,Iguchi A,Nabeshima T

    更新日期:1996-09-27 00:00:00

  • Polyunsaturated fatty acids reduce pyrogen-induced tissue factor expression in human monocytes.

    abstract::Endotoxin (LPS) and interleukin-1 beta (IL-1 beta) increased the expression of tissue factor, a membrane-anchored glycoprotein that initiates blood coagulation on the surface of cultured human umbilical vein endothelial cells (HUVEC) and human monocyte/macrophages. On monocyte/macrophages, oleic acid strongly inhibite...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Lalé A,Herbert JM

    更新日期:1994-07-19 00:00:00

  • Solubilization of active somatostatin receptors from rabbit retina.

    abstract::Somatostatin receptors from rabbit retinal membranes were solubilized in an active form using a mixture of the detergent n-octyl b-D-glucopyranoside (OG) and CHAPS. The binding of [125I]-Try11-somatostatin to the soluble extract was saturable and of high affinity, with an apparent affinity constant (Kd) of 0.60 +/- 0....

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Liapakis G,Politou E,Thermos K

    更新日期:1993-05-05 00:00:00

  • Anthracycline resistance in murine leukemic P388 cells. Role of drug efflux and glutathione related enzymes.

    abstract::Energy-dependent drug efflux is a major factor in cellular resistance of P388/R84 mouse leukemic cells to anthracyclines such as doxorubicin (DOX), and blocking of efflux increases sensitivity. However, efflux does not play a significant role in resistance to N-trifluoroacetyladriamycin-14-valerate (AD 32), a DOX anal...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Nair S,Singh SV,Samy TS,Krishan A

    更新日期:1990-02-15 00:00:00

  • Secretory phospholipase A2 enzymes as pharmacological targets for treatment of disease.

    abstract::Phospholipase A2 (PLA2) cleave phospholipids preferentially at the sn-2 position, liberating free fatty acids and lysophospholipids. They are classified into six main groups based on size, location, function, substrate specificity and calcium requirement. These classes include secretory PLA2 (sPLA2), cytosolic (cPLA2)...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章,评审


    authors: Quach ND,Arnold RD,Cummings BS

    更新日期:2014-08-15 00:00:00

  • Electron paramagnetic resonance spectrometry evidence for bioreduction of tirapazamine to oxidising free radicals under anaerobic conditions.

    abstract::Tirapazamine (SR 4233) is a bioreductive antitumour drug in Phase III clinical trial which is activated in hypoxic tumour regions to generate a cytotoxic species. Electron paramagnetic resonance (EPR) spectrometry was used to investigate directly the formation of free radicals as the result of tirapazamine reduction b...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Patterson LH,Taiwo FA

    更新日期:2000-12-15 00:00:00

  • Relative contribution of rat cytochrome P450 isoforms to the metabolism of caffeine: the pathway and concentration dependence.

    abstract::The aim of the present study was to estimate the relative contribution of rat P450 isoforms to the metabolism of caffeine and to assess the usefulness of caffeine as a marker substance for estimating the activity of P450 in rat liver and its potential for pharmacokinetic interactions in pharmacological experiments. Th...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Kot M,Daniel WA

    更新日期:2008-04-01 00:00:00

  • Coordinate regulation between the nuclear receptor peroxisome proliferator-activated receptor-γ and cyclooxygenase-2 in renal epithelial cells.

    abstract::The peroxisome proliferator-activated receptors (PPARs) are ligand-dependent transcription factors involved in lipid metabolism and glucose utilization, in cell growth, differentiation and apoptosis, and in the regulation of pro-inflammatory genes expression such as cyclooxygenase-2 (COX-2). PPARγ is the main isoform ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Casali CI,Weber K,Faggionato D,Gómez EM,Tome MC

    更新日期:2014-08-15 00:00:00

  • Hepatic subcellular localization of cresylbenzodioxaphosphorin oxide (CBDP)-sensitive soman binding sites.

    abstract::The toxicity of the organophosphorus poison soman (pinacolylmethylphosphonofluoridate) is attributable to its irreversible inhibition of the enzyme acetylcholinesterase. In addition, soman binds irreversibly to a number of noncholinesterase tissue binding sites which appear to be its major means of in vivo detoxificat...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Little JS,Maxwell DM,Fox-Talbot MK,Brecht K,Lenz DE

    更新日期:1990-10-15 00:00:00

  • Angiotensin II promotes pulmonary metastasis of melanoma through the activation of adhesion molecules in vascular endothelial cells.

    abstract::Hypertension is considered as one of the cancer progressive factors, and often found comorbidity in cancer patients. Renin-angiotensin system (RAS) plays an important role in the regulation of blood pressure, and angiotensin II (Ang II) is well known pressor peptide associated with RAS. Ang II has been reported to acc...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Ishikane S,Hosoda H,Nojiri T,Tokudome T,Mizutani T,Miura K,Akitake Y,Kimura T,Imamichi Y,Kawabe S,Toyohira Y,Yanagihara N,Takahashi-Yanaga F,Miyazato M,Miyamoto K,Kangawa K

    更新日期:2018-08-01 00:00:00

  • Effect of tuamine, heptaminol and two analogues on uptake and release of catecholamines in cultured chromaffin cells.

    abstract::The effects of tuamine (1-methylhexylamine), a sympathomimetic compound with hypertensive properties, heptaminol (6-amino-2-methyl-2-heptanol), an aliphatic amine with pressor properties, and two structural analogues of tuamine on high-affinity Na(+)-dependent noradrenaline uptake and on nicotine-evoked release were e...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Delicado EG,Fideu MD,Miras-Portugal MT,Pourrias B,Aunis D

    更新日期:1990-08-15 00:00:00

  • Cellular distribution of N-acetyltransferase activity in the rat small intestine.

    abstract::The cellular distribution of AcCoA:arylamine N-acetyltransferase (NAT; EC activities was examined in the rat small intestine to determine if heterogeneous cellular distribution contributes to preferential tumor development in the colonic region after exposure to heterocyclic amines (HAs). A chelation/elution ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Ware JA,Reilly TP,Svensson CK

    更新日期:1998-05-01 00:00:00

  • Homo- and hetero-dimerization of human UDP-glucuronosyltransferase 2B7 (UGT2B7) wild type and its allelic variants affect zidovudine glucuronidation activity.

    abstract::Most human UDP-glucuronosyltransferase (UGT; EC genes contain non-synonymous single nucleotide polymorphisms (nsSNPs) which cause amino acid substitutions. Allelic variants caused by nsSNPs may exhibit absent or reduced enzyme activity. UGT2B7 is one of the most important UGTs that glucuronidates abundant en...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Yuan L,Qian S,Xiao Y,Sun H,Zeng S

    更新日期:2015-05-01 00:00:00

  • Formation and retention and biological activity of N10-propargyl-5,8-dideazafolic acid (CB3717) polyglutamates in L1210 cells in vitro.

    abstract::The formation, retention and biological activity of the polyglutamate metabolites of the thymidylate synthase (TS) inhibitor N10-propargyl-5,8-dideazafolic acid (CB3717) has been investigated in L1210 murine leukaemia cells grown in vitro. CB3717 polyglutamates were measured by HPLC using high specific activity 3H-CB3...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Sikora E,Jackman AL,Newell DR,Calvert AH

    更新日期:1988-11-01 00:00:00

  • Regulation of interleukin-13 by type 4 cyclic nucleotide phosphodiesterase (PDE) inhibitors in allergen-specific human T lymphocyte clones.

    abstract::Interleukin-13 (IL-13) is a proinflammatory cytokine of T cell origin. Structural and functional studies suggest a key role for IL-13 in the genesis of chronic allergic inflammation; as such, its pharmacologic inhibition is of potential clinical utility. We studied the pharmacologic regulation of IL-13 expression by c...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Essayan DM,Kagey-Sobotka A,Lichtenstein LM,Huang SK

    更新日期:1997-04-04 00:00:00

  • The Bcr-Abl inhibitor GNF-7 inhibits necroptosis and ameliorates acute kidney injury by targeting RIPK1 and RIPK3 kinases.

    abstract::Necroptosis is a form of programmed, caspase-independent cell death that is involved in various pathologic disorders such as ischemia/reperfusion injury, acute kidney injury and inflammatory bowel diseases. Identification of necroptosis inhibitors has great therapeutic potential for the treatment of necroptosis-associ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Qin X,Hu L,Shi SN,Chen X,Zhuang C,Zhang W,Jitkaew S,Pang X,Yu J,Tan YX,Wang HY,Cai Z

    更新日期:2020-07-01 00:00:00

  • Ferredoxin-dependent reduction of nitroimidazole derivatives in drug-resistant and susceptible strains of Trichomonas vaginalis.

    abstract::The inhibitory effect of a range of nitroimidazole-derivatives on H2 production by metronidazole resistant (CDC-85) and susceptible (C1-NIH) Trichomonas vaginalis strains was investigated. The 2-, 4-, and 5-nitro-derivatives used had one-electron reduction potentials within the range -250 to -525 mV. Nitroimidazole co...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Yarlett N,Yarlett NC,Lloyd D

    更新日期:1986-05-15 00:00:00

  • Flavin-dependent antioxidant properties of a new series of meso-N,N'-dialkyl-imidazolium substituted manganese(III) porphyrins.

    abstract::A number of synthetic manganese complexes exhibit both in vitro and in vivo catalytic antioxidant activities. This study reports that the antioxidant potencies of a new series of meso-N,N'-dialkyl-imidazolium substituted manganese(III) porphyrins are dependent, in part, on their ability to redox cycle with endogenous ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Kachadourian R,Johnson CA,Min E,Spasojevic I,Day BJ

    更新日期:2004-01-01 00:00:00

  • Thiourea toxicity in mouse C3H/10T1/2 cells expressing human flavin-dependent monooxygenase 3.

    abstract::Human flavin-dependent monooxygenase (FMO) isoforms 1 and 3 were expressed by retroviral gene transfer in mouse C3H/10T1/2 cells. FMO function was determined by the sulfoxidation of p-tolylmethylsulfide (TMS). Enzyme activity ranged from 4 to 30 nmol p-tolylmethylsulfoxide (TMSO)/30 min/mg cell protein for FMO 3 clone...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Smith PB,Crespi C

    更新日期:2002-06-01 00:00:00

  • Evaluation of estrogen receptor, antiestrogen binding sites and calmodulin for antiestrogen resistance of two clones derived from the MCF-7 breast cancer cell line.

    abstract::Estrogen receptor (ER), antiestrogen binding sites (AEBS) and calmodulin (CaM) are potential targets of antiestrogen (AE) action. To analyse further which of these targets are primarily involved in the antiproliferative activity of these drugs against human breast cancers, two cell clones, namely the RTx6 and LY-2 var...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Borras M,Jin L,Bouhoute A,Legros N,Leclercq G

    更新日期:1994-11-29 00:00:00

  • Ascorbic acid: an endogenous inhibitor of isolated Na+,K+-ATPase.

    abstract::During attempts to isolate and identify an endogenous ligand for the glycoside binding sites on Na+,K+-ATPase, bovine adrenal glands were found to contain a potent inhibitor of isolated Na+,K+-ATPase. The inhibitory principle was extracted from adrenal cortex, following homogenization in NaHCO3 solution and separation...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Ng YC,Akera T,Han CS,Braselton WE,Kennedy RH,Temma K,Brody TM,Sato PH

    更新日期:1985-07-15 00:00:00

  • The signalling axis mediating neuronal apoptosis in response to [Pt(O,O'-acac)(γ-acac)(DMS)].

    abstract::It was previously shown that [Pt(O,O'-acac)(γ-acac)(DMS)] induces apoptosis in various cancer cells and exerts antimetastatic responses in vitro. In rats, [Pt(O,O'-acac)(γ-acac)(DMS)] reaches the central nervous system in quantities higher than cisplatin causing less excitotoxicity. The aim of the present paper was to...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Muscella A,Calabriso N,Vetrugno C,Fanizzi FP,De Pascali SA,Marsigliante S

    更新日期:2011-06-01 00:00:00

  • 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


    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

  • Functional elements of the gastric inhibitory polypeptide receptor: Comparison between secretin- and rhodopsin-like G protein-coupled receptors.

    abstract::Innovative crystallographic techniques have resulted in an exponential growth in the number of solved G-protein coupled receptor (GPCR) structures and a better understanding of the mechanisms of class A receptor activation and G protein binding. The recent release of the type 1 receptor for the corticotropin-releasing...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Cordomí A,Ismail S,Matsoukas MT,Escrieut C,Gherardi MJ,Pardo L,Fourmy D

    更新日期:2015-08-01 00:00:00

  • Endogenous monoamine oxidase inhibitor-like substances in monkey brain.

    abstract::The extraction and partial purification of endogenous "monoamine oxidase (MAO) inhibitor-like" material from the monkey brain are described. The endogenous material (F-1 and F-2) obtained after Bio-Gel P-2 gel filtration and silica column chromatography inhibited MAO in the monkey brain mitochondria toward 5-hydroxytr...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Egashira T,Obata T,Nagai T,Kimba Y,Takano R,Yamanaka Y

    更新日期:1989-02-15 00:00:00

  • Inactivation of mouse epidermal 12-lipoxygenase by anthralin--implications for the role of oxygen radicals.

    abstract::In activation of 12-lipoxygenase (12-LO) in mouse epidermal homogenate by the antipsoriatic drug anthralin has been studied in detail. In view of the chemical instability of anthralin in a physiological buffer, the biological effects ascribed to the molecule itself may be related to some of its breakdown products. How...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Müller K,Gawlik I

    更新日期:1996-05-03 00:00:00

  • Oxidative activation of 2-aminofluorene by human red blood cell cytosol.

    abstract::Purified red blood cell cytosol is able to activate 2-aminofluorene (2AF) to N-hydroxy-2-aminofluorene. Apparent kinetic parameters are determined with and without methylene blue. The latter, which maintains haemoglobin in the reduced form and stimulates NADPH production, increases the affinity of the enzyme for the 2...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Duverger-van Bogaert M,Wiame D,Stecca C

    更新日期:1992-12-15 00:00:00

  • Influence of chronic administration of valproate on ultrastructure and enzyme content of peroxisomes in rat liver and kidney. Oxidation of valproate by liver peroxisomes.

    abstract::Chronic administration to rats of the anticonvulsant drug, valproate, induced proliferation of liver peroxisomes and selectively increased the activity of the enzymes involved in beta-oxidation in these organelles. In kidney cortex, only a moderate increase in enzyme activity could be recorded. Valproate (1% w/w in th...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Ponchaut S,Draye JP,Veitch K,Van Hoof F

    更新日期:1991-05-15 00:00:00