The preferential homing of a platelet derived growth factor receptor-recognizing macromolecule to fibroblast-like cells in fibrotic tissue.


:Platelet derived growth factor (PDGF) is a key factor in the induction and progression of fibrotic diseases with the activated fibroblast as its target cell. Drug targeting to the PDGF-receptor is explored as a new approach to treat this disease. Therefore, we constructed a macromolecule with affinity for the PDGF-beta receptor by modification of albumin with a small peptide that recognises this PDGF-beta receptor. The binding of the peptide-modified albumin (pPB-HSA) to the PDGF-beta receptor was confirmed in competition studies with PDGF-BB using NIH/3T3-fibroblasts and activated hepatic stellate cells. Furthermore, pPB-HSA was able to reduce PDGF-BB-induced fibroblast proliferation in vitro, and proved to be devoid of proliferation-inducing activity itself. We assessed the distribution of pPB-HSA in vivo in two models of fibrosis and related the distribution of pPB-HSA to PDGF-beta receptor density. In rats with liver fibrosis (bile duct ligation model), pPB-HSA quickly accumulated in the liver in contrast to unmodified HSA (P<0.001). The major part of pPB-HSA in the fibrotic liver was localized in hepatic stellate cells. In rats with renal fibrosis (anti-Thy1.1 model), pPB-HSA also homed to the cells that expressed the PDGF-beta receptor, i.e. the mesangial cells in the glomeruli of the kidney. These results indicate that pPB-HSA may be applied as a macromolecular drug-carrier that accumulates specifically in cells expressing the PDGF-beta receptor, thus allowing a selective delivery of anti-fibrotic agents to these cells.


Biochem Pharmacol


Biochemical pharmacology


Beljaars L,Weert B,Geerts A,Meijer DK,Poelstra K




Has Abstract


2003-10-01 00:00:00














  • Comparison of the effects of bupropion and nicotine on locomotor activation and dopamine release in vivo.

    abstract::Bupropion is an atypical anti-depressant that is approved for smoking cessation. In addition to inhibiting dopamine reuptake, bupropion has been reported to block nicotinic acetylcholine receptors in vitro, and this action might contribute to its efficacy for smoking cessation. In this study we investigated if nicotin...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Sidhpura N,Redfern P,Rowley H,Heal D,Wonnacott S

    更新日期:2007-10-15 00:00:00

  • Characterization of the muscarinic receptor subtype in isolated gastric fundic cells of the rabbit.

    abstract::The characteristics of the muscarinic receptor in isolated gastric fundic cells from rabbit were determined by radioligand binding techniques and functional tests. The dissociation constants (KDS) of selective (hexahydrosiladifenidol and pirenzepine) and non-selective (N-methylscopolamine and atropine) muscarinic rece...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Baudiere B,Monferini E,Giraldo E,Ladinsky H,Bali JP

    更新日期:1987-09-15 00:00:00

  • Actin cytoskeleton, tubular sodium and the renal synthesis of dopamine.

    abstract::The present study has examined the effect of colchicine and cytochalasin B, two cytoskeleton disrupter compounds, on the formation of dopamine in slices of rat renal cortex loaded with exogenous L-3,4-dihydroxyphenylalanine (L-DOPA); the deamination of newly formed dopamine into 3,4-dihydroxyphenylacetic acid (DOPAC) ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Soares-da-Silva P

    更新日期:1992-11-03 00:00:00

  • Methotrexate analogues--XVII. Antitumor activity of 4-amino-4-deoxy-N10-methylpteroyl-D,L-homocysteic acid and its dual inhibition of dihydrofolate reductase and folyl polyglutamate synthetase.

    abstract::A new analogue of methotrexate was synthesized from 4-amino-4-deoxy-N10-methylpteroic acid and D,L-homocysteic acid. The product (mAPA-HCysA) was bound tightly to L1210 mouse leukemia dihydrofolate reductase (IC50 = 1 nM), inhibited L1210 cell proliferation in culture (IC50 = 0.3 microM), and prolonged the survival of...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Rosowsky A,Moran RG,Forsch R,Colman P,Uren J,Wick M

    更新日期:1984-01-01 00:00:00

  • Protein kinase Cδ mediates the activation of protein kinase D2 in platelets.

    abstract::Protein kinase D (PKD) is a subfamily of serine/threonine specific family of kinases, comprised of PKD1, PKD2 and PKD3 (PKCμ, PKD2 and PKCv in humans). It is known that PKCs activate PKD, but the relative expression of isoforms of PKD or the specific PKC isoform/s responsible for its activation in platelets is not kno...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Bhavanasi D,Kim S,Goldfinger LE,Kunapuli SP

    更新日期:2011-10-01 00:00:00

  • Impairment of bromosulfophthalein hepatic transport and cholestasis induced by diethyl maleate in the rabbit.

    abstract::The present study was designed to investigate the effect of hepatic glutathione depletion induced by intraperitoneal administration of diethyl maleate (DEM) on the maximum biliary transport (Tm) and on the biliary excretion of bromosulfophthalein (BSP) in anaesthetized rabbits when the dye was perfused endovenously at...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Jiménez R,Larrubia O,Monte MJ,Esteller A

    更新日期:1988-04-01 00:00:00

  • Drug metabolism in cirrhosis. Selective changes in cytochrome P-450 isozymes in the choline-deficient rat model.

    abstract::The effect of a choline-deficient diet on microsomal cytochrome P-450 and mixed-function oxidase (MFO) activity was investigated in relation to the development of nutritional cirrhosis. In rats that received the choline-deficient diet for 28 weeks cirrhosis was evident macroscopically and histologically; control rats ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Murray M,Zaluzny L,Farrell GC

    更新日期:1986-06-01 00:00:00

  • Fatty acid acylation of mucin by gastric mucosa: effects of sofalcone and sucralfate.

    abstract::The effects of antiulcer drugs, sofalcone and sucralfate, on the activity of gastric mucosal mucus glycoprotein fatty acyltransferase were investigated. The acyltransferase enzyme, contained in the detergent extracts of the microsomal fraction of rat gastric mucosa, was incubated with the deacylated gastric mucin and ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Slomiany BL,Liau YH,Mizuta K,Slomiany A

    更新日期:1987-10-01 00:00:00

  • Differential effect of simvastatin on various signal transduction intermediates in cultured human smooth muscle cells.

    abstract::The underlying mechanism of the antiproliferative effect of S (simvastatin), a HMG-CoA reductase inhibitor, in vascular smooth muscle cells (SMC) is still poorly understood. In the present study, we used synchronized human SMC, isolated from left interior mammary artery, as an in vitro model to test the effects of S o...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Nègre-Aminou P,van Erck M,van Leeuwen RE,Collard JG,Cohen LH

    更新日期:2001-04-15 00:00:00

  • Effects of iron deprivation on the pathology and stress protein expression in murine X-linked muscular dystrophy.

    abstract::Duchenne muscular dystrophy (DMD) is caused by dystrophin deficiency, which results in muscle necrosis and the upregulation of heat shock/stress proteins (HSP). We hypothesized that reactive oxygen species, and in particular hydroxyl radicals (.OH), participate in muscle necrosis and HSP expression. It was assumed tha...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Bornman L,Rossouw H,Gericke GS,Polla BS

    更新日期:1998-09-15 00:00:00

  • (D-Ser2)Oxm[mPEG-PAL]: a novel chemically modified analogue of oxyntomodulin with antihyperglycaemic, insulinotropic and anorexigenic actions.

    abstract::Oxyntomodulin (Oxm) is a hormone which has been shown to exhibit a range of potentially beneficial actions for alleviation of obesity-diabetes. However, exploitation of Oxm-based therapies has been severely restricted due to degradation by the enzyme dipeptidylpeptidase-IV (DPP-IV). Thus, the aim of this study was to ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Kerr BD,Flatt PR,Gault VA

    更新日期:2010-12-01 00:00:00

  • Mechanisms of toxicity of 3'-azido-3'-deoxythymidine. Its interaction with adenylate kinase.

    abstract::Recent experiments from our laboratory have indicated that the inhibitory effect of 3'-azido-3'-deoxythymidine (AZT) on oxidative phosphorylation may occur directly, in addition to being brought about by its inhibition of mtDNA replication. We report here studies on the effect of AZT on adenylate kinase, an enzyme cru...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Barile M,Valenti D,Hobbs GA,Abruzzese MF,Keilbaugh SA,Passarella S,Quagliariello E,Simpson MV

    更新日期:1994-10-07 00:00:00

  • Effects of the peroxisome proliferator mono(2-ethylhexyl)phthalate in primary hepatocyte cultures derived from rat, guinea pig, rabbit and monkey. Relationship between interspecies differences in biotransformation and peroxisome proliferating potencies.

    abstract::Primary hepatocyte cultures derived from rat, rabbit, guinea pig and monkey have been treated in vitro with metabolites of di(2-ethylhexyl)phthalate, i.e. mono(2-ethylhexyl)phthalate (MEHP), mono(5-carboxy-2-ethylpentyl)phthalate (metabolite V) and mono(2-ethyl-5-oxohexyl)phthalate (metabolite VI). In rat hepatocyte c...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Dirven HA,van den Broek PH,Peeters MC,Peters JG,Mennes WC,Blaauboer BJ,Noordhoek J,Jongeneelen FJ

    更新日期:1993-06-22 00:00:00

  • Morphine is a substrate of the organic cation transporter OCT1 and polymorphisms in OCT1 gene affect morphine pharmacokinetics after codeine administration.

    abstract::We investigated whether morphine and its pro-drug codeine are substrates of the highly genetically polymorphic organic cation transporter OCT1 and whether OCT1 polymorphisms may affect morphine and codeine pharmacokinetics in humans. Morphine showed low transporter-independent membrane permeability (0.5 × 10⁻⁶ cm/s). ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Tzvetkov MV,dos Santos Pereira JN,Meineke I,Saadatmand AR,Stingl JC,Brockmöller J

    更新日期:2013-09-01 00:00:00

  • Antitumour imidazotetrazines--IV. An investigation into the mechanism of antitumour activity of a novel and potent antitumour agent, mitozolomide (CCRG 81010, M & B 39565; NSC 353451).

    abstract::8-Carbamoyl-3-(2-chloroethyl)imidazo[5,1-d]-1,2,3,5-tetrazin-4-(3H )-one- mitozolomide (CCRG 81010, M & B 39565, NSC 353451) is a potent inhibitor of the growth of a number of experimental tumours and can potentially decompose to give either an isocyanate or the monochloroethyltriazene (MCTIC). In vitro CCRG 81010 is ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Horgan CM,Tisdale MJ

    更新日期:1984-07-15 00:00:00

  • Potentiation of the biochemical effects of beta-phenylethylhydrazine by deuterium substitution.

    abstract::The concentrations of dopamine (DA), m-tyramine (mTA), p-tyramine (pTA) and serotonin (5-HT) in the striata of rats 18 hr after the administration of three different doses (5, 50, or 100 mg/kg) of beta-phenylethylhydrazine (phenelzine, PEH) were measured. These concentrations were compared to those following the admin...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Dyck LE,Durden DA,Yu PH,Davis BA,Boulton AA

    更新日期:1983-05-01 00:00:00

  • Evidence for ryanodine receptors in Schistosoma mansoni.

    abstract::The present study investigated the presence of ryanodine receptors in the trematode Schistosoma mansoni. [3H]Ryanodine specific binding sites were found in the four subcellular fractions of S. mansoni; however, more binding sites were recovered in the heterogeneous fraction P1 and the microsomal fraction P4, as was th...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Silva CL,Cunha VM,Mendonça-Silva DL,Noël F

    更新日期:1998-10-15 00:00:00

  • Biotransformation of 17 beta-hydroxy-11 beta-(4-dimethylaminophenyl)17 alpha-1-propynyl-estra-4,9-dien-3-one (RU486) in rat hepatoma variants.

    abstract::Metabolism of the synthetic steroid 17 beta-hydroxy-11 beta-(4-dimethylaminophenyl)17 alpha-1-propynyl-estra-4,9-dien-3-one (RU486) occurs in the dedifferentiated S-H56-125 variant of Reuber hepatoma. Considering that rat liver cytochrome P450 (P450) monooxygenases are engaged in different oxidative steps of the metab...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Chasserot-Golaz S,Beck G,Venetianer A

    更新日期:1993-12-03 00:00:00

  • Inversely-correlated inhibition of human 5-lipoxygenase activity by BAY X1005 and other quinoline derivatives in intact cells and a cell-free system--implications for the function of 5-lipoxygenase activating protein.

    abstract::A series of quinoline derivatives were analysed for the influence on leukotriene synthesis as a parameter for 5-LOX (EC activity in a cell-free system of the 10,000 g supernatant of human PMNL (polymorphonuclear leukocytes). The ratios of the IC50 values for leukotriene synthesis inhibition in this cell-fr...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Hatzelmann A,Goossens J,Fruchtmann R,Mohrs KH,Raddatz S,Müller-Peddinghaus R

    更新日期:1994-06-15 00:00:00

  • Effects of the beta 2-adrenoceptor agonist clenbuterol on tyrosine and tryptophan in plasma and brain of the rat.

    abstract::The beta 2-adrenoceptor agonist, clenbuterol (initially 5 mg/kg), was found to significantly reduce plasma tyrosine and raise brain tryptophan levels (P less than 0.01). By comparison, decreases in plasma tryptophan and increases in brain tyrosine were small and often nonsignificant. Amino acid levels measured in diff...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Edwards DJ,Sorisio DA,Knopf S

    更新日期:1989-09-15 00:00:00

  • Inhibition of NADPH-cytochrome P450 reductase and glyceryl trinitrate biotransformation by diphenyleneiodonium sulfate.

    abstract::We reported previously that the flavoprotein inhibitor diphenyleneiodonium sulfate (DPI) irreversibly inhibited the metabolic activation of glyceryl trinitrate (GTN) in isolated aorta, possibly through inhibition of vascular NADPH-cytochrome P450 reductase (CPR). We report that the content of CPR represents 0.03 to 0....

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: McGuire JJ,Anderson DJ,McDonald BJ,Narayanasami R,Bennett BM

    更新日期:1998-10-01 00:00:00

  • Pitfalls in demonstrating an endogenous ligand of imipramine recognition sites.

    abstract::The recognition sites for the 5-hydroxytryptamine (5-HT) uptake inhibitors imipramine and paroxetine may represent receptors for a presently unknown endogenous ligand, whose function would be to modulate 5-HT uptake. Attempts to isolate such a factor from rat brain tissue are described, following a published procedure...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Lee CR,Galzin AM,Taranger MA,Langer SZ

    更新日期:1987-03-15 00:00:00

  • Inhibition of calmodulin-activated cyclic nucleotide phosphodiesterase: multiple binding-sites for tricyclic drugs on calmodulin.

    abstract::A cyclic nucleotide phosphodiesterase from guinea-pig heart is activated by calmodulin in the presence of calcium ions. Activation was measured over a range of calmodulin concentrations, and is antagonised by several tricyclic psychotropic drugs including trifluoperazine, imipramine, chlorpromazine and amitriptyline. ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Reynolds CH,Claxton PT

    更新日期:1982-02-01 00:00:00

  • Role of adrenoceptor-linked signaling pathways in the regulation of CYP1A1 gene expression.

    abstract::Alpha2-adrenoceptor agents as well as stress affect the activity of several hepatic monoxygenases including those related to CYP1A enzymes. This study was therefore designed to assess the role of central and/or peripheral catecholamines and, in particular, of adrenoceptors in the regulation of B(alpha)P-induced cytoch...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Konstandi M,Kostakis D,Harkitis P,Marselos M,Johnson EO,Adamidis K,Lang MA

    更新日期:2005-01-15 00:00:00

  • Benzylamide derivative compound attenuates the ultraviolet B-induced hyperpigmentation in the brownish guinea pig skin.

    abstract::This study evaluated the effects of synthetic benzylamide compound I (2,6-dimethoxy-N-phenylbenzamide) on the ultraviolet B (UV B)-induced hyperpigmentation of the skin. UV B-induced hyperpigmentation was elicited on brownish guinea pig skin according to the method reported by Hideya et al. [Arch Dermatol Res 290 (199...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Choi SY,Kim S,Hwang JS,Lee BG,Kim H,Kim SY

    更新日期:2004-02-15 00:00:00

  • Inverse gene expression patterns for macrophage activating hepatotoxicants and peroxisome proliferators in rat liver.

    abstract::Macrophage activation contributes to adverse effects produced by a number of hepatotoxic compounds. Transcriptional profiles elicited by two macrophage activators, LPS and zymosan A, were compared to those produced by 100 paradigm compounds (mostly hepatotoxicants) using cDNA microarrays. Several hepatotoxicants previ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: McMillian M,Nie AY,Parker JB,Leone A,Kemmerer M,Bryant S,Herlich J,Yieh L,Bittner A,Liu X,Wan J,Johnson MD

    更新日期:2004-06-01 00:00:00

  • Mechanism of inhibition of hepatic bile acid uptake by amiloride and 4,4'-diisothiocyano-2,2'-disulfonic stilbene (DIDS).

    abstract::The mechanisms by which amiloride and 4,4'-diisothiocyano-2,2'-disulfonic stilbene (DIDS) inhibit hepatic uptake of cholate and taurocholate (TC) were investigated in isolated rat hepatocytes. Amiloride inhibited Na(+)-dependent uptake of cholate and TC only when hepatocytes were preincubated with amiloride, indicatin...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Anwer MS,Branson AU,Atkinson JM

    更新日期:1991-12-11 00:00:00

  • Selective early loss of polypeptides in liver microsomes of CCl4-treated rats. Relationship to cytochrome P-450 content.

    abstract::Treatment of rats with carbon tetrachloride (CCl4) resulted in early reproducible losses of either one or two specific polypeptides (depending on the inducing agent with which the animals had been treated) in the molecular weight range of the multiple forms of cytochrome P-450. The loss was correlated with a decrease ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Noguchi T,Fong KL,Lai EK,Olson L,McCay PB

    更新日期:1982-03-01 00:00:00

  • The bone marrow microenvironment as a sanctuary for minimal residual disease in CML.

    abstract::Bcr-abl kinase inhibitors have provided proof of principal that targeted therapy holds great promise for the treatment of cancer. However, despite the success of these agents in treating chronic myelogenous leukemia (CML), the majority of patients continue to present with minimal residual disease contained within the ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章,评审


    authors: Nair RR,Tolentino J,Hazlehurst LA

    更新日期:2010-09-01 00:00:00

  • Protein S-glutathionylation and platelet anti-aggregating activity of disulfiram.

    abstract::Blood platelets are central to haemostasis, and reactions in platelets involving sulfhydryl groups play important roles in platelet function. Reduced glutathione (GSH) plays an important role in platelet aggregation and glutathione-depleting chemicals inhibit platelet aggregation. The lipophilic drug disulfiram, becau...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Rossi R,Giustarini D,Dalle-Donne I,Milzani A

    更新日期:2006-08-28 00:00:00