Search results for "TRANSPORTER"
showing 10 items of 676 documents
Relevancia clínica de la selectividad de los inhibidores del cotransportador sodio-glucosa tipo 2
2016
Selectivity is the property of a drug to preferentially bind to a biological structure. Most drugs can bind and stimulate or inhibit more than one system. Therefore, it is important that they are selective for the intended site and that the doses used do not have effects on other sites, which could provoke adverse reactions. Selectivity is assessed through in vitro experiments on organs or isolated cells. If the aim is to compare drugs, the experiment should be conducted in the same tissue and with the same design. Even so, the results cannot be directly extrapolated to clinical practice due to the influence of pharmacokinetic properties, which allow an adequate dose of the drug to reach th…
Intracellular retention of ABL kinase inhibitors determines commitment to apoptosis in CML cells
2012
PLoS one 7(7), e40853 (2012). doi:10.1371/journal.pone.0040853
The multixenobiotic resistance mechanism in the marine sponge Suberites domuncula: its potential applicability for the evaluation of environmental po…
1996
Experiments were carried out with the marine sponge Suberites domuncala to determine whether sponges may express - like mammalian tumor cells a multidrug-like transporter system. The results demonstrate that sponge cells possess such a protective system termed multixenobiotic resistance (MXR) pump or P-glycoprotein-like pump, The protein was identified by antisera for the mammalian P170 multidrug resistance protein as a 130 kDa molecule, Binding studies were performed with H-3-vincristine (H-3-VCR) and membrane vesicles ; this process is ATP-dependent and inhibited by verapamil, which is known to reverse the multidrug-resistance phenotype in mammalian systems, Accumulation experiments were …
Involvement of carboxyl groups in chloride transport and reversible DIDS binding to band 3 protein in human erythrocytes
2011
AbstractNoncovalent DIDS binding to Band 3 (AE1) protein in human erythrocyte membranes, modified by non-penetrating, water soluble 1-ethyl-3-(4-azonia-4,4-dimethylpentyl)-carbodiimide iodide (EAC), was studied at 0°C in the presence of 165 mM KCl. Under experimental conditions applied up to (48 ± 5) % of irreversible chloride self-exchange inhibition was observed. The apparent dissociation constant, KD, for “DIDS-Band 3” complex, determined from the chloride transport experiments, was (34 ± 3) nM and (80 ± 12) nM for control and EAC-treated resealed ghosts, respectively. The inhibition constant, Ki, for DIDS was (35 ± 6) nM and (60 ± 8) nM in control and EAC-treated ghosts, respectively. T…
Expression of Active Streptolysin O in Escherichia coli as a Maltose-Binding-Protein-Streptolysin-O Fusion Protein. The N-Terminal 70 Amino Acids are…
1996
Streptolysin 0 (SLO) is the prototype of a family of cytolysins that consists of proteins which bind to cholesterol and form very large transmembrane pores. Structure/function studies on the pore-forming cytolysin SLO have been complicated by the proteolytic inactivation of a substantial portion of recombinant SLO (rSLO) expressed in Escherichia coli. To overcome this problem, translational fusions between the E. coli maltose-binding protein (MBP) gene and SLO were constructed, using the vectors pMAL-p2 and pMAL-c2. MBP-SLO fusion proteins were degraded if secreted into the E. coli periplasm, but intact, soluble MBP-SLO fusion proteins were produced at high levels in the cytoplasm. Active S…
Production of neutron deficient rare isotope beams at IGISOL; on-line and off-line studies
2004
This article reports on recent on-line yield measurements employing the light-ion and heavy-ion reaction-based ion guide systems and new results on a-recoil ion transport properties in ion guides with and without electric fields. In addition, the presently used ion guide designs for fusion evaporation reactions are introduced. The present study investigated different schemes for ion extraction from the gas cell. The addition of an extra ring electrode between the traditional skimmer electrode and the exit hole led to transmission independent of the primary beam intensity as opposed to strong intensity dependence observed earlier with the plain skimmer only. Furthermore, the mass resolving p…
Polymorphisms in ABC transporter genes and concentrations of mercury in newborns - Evidence from two Mediterranean birth cohorts
2014
Background: The genetic background may influence methylmercury (MeHg) metabolism and neurotoxicity. ATP binding cassette (ABC) transporters actively transport various xenobiotics across biological membranes. Objective: To investigate the role of ABC polymorphisms as modifiers of prenatal exposure to MeHg. Methods: The study population consisted of participants (n = 1651) in two birth cohorts, one in Italy and Greece (PHIME) and the other in Spain (INMA). Women were recruited during pregnancy in Italy and Spain, and during the perinatal period in Greece. Total mercury concentrations were measured in cord blood samples by atomic absorption spectrometry. Maternal fish intake during pregnancy w…
Bidirectional membrane transport: Simulations of transport inhibition in uptake studies explain data obtained with flavonoids
2006
The purpose of the simulations was to obtain an estimate of concentration-dependent uptake curves when two counteracting transporters are present. On the basis of this experimental data obtained with a pair of ovarian carcinoma cell lines, one of which was not expressing the exsorptive transporter P-glycoprotein and one of which was an MDR1-transfected, P-glycoprotein expressing variant, the kinetics of cellular uptake of the radiolabel (3)H-talinolol were calculated and the inhibitory constants at P-gp were determined for different flavonoids. With respect to the inhibition of P-gp function, among others, naringenin and isoquercitrin were identified as inhibitors, yet estimation of the inh…
Evaluation of P-glycoprotein (abcb1a/b) modulation of [18F]fallypride in MicroPET imaging studies
2012
[(18)F]Fallypride ([(18)F]FP) is an important and routinely used D2/D3 antagonist for quantitative imaging of dopaminergic neurotransmission in vivo. Recently it was shown that the brain uptake of the structurally related [(11)C]raclopride is modulated by P-glycoprotein (P-gp), an important efflux transporter at the blood-brain barrier. The purpose of this study was to determine whether the brain uptake of [(18)F]FP is influenced by P-gp. For examination of this possible modulation microPET studies were performed in a rat and a mouse model. Hence, [(18)F]FP was applied to Sprague Dawley rats, half of them being treated with the P-gp inhibitor cyclosporine A (CsA). In a second experimental s…
Synthesis and evaluation of (S)-2-(2-[18F]fluoroethoxy)-4-([3-methyl-1-(2-piperidin-1-yl-phenyl)-butyl-carbamoyl]-methyl)-benzoic acid ([18F]repaglin…
2004
18F-labeled non-sulfonylurea hypoglycemic agent (S)-2-(2-[(18)F]fluoroethoxy)-4-((3-methyl-1-(2-piperidin-1-yl-phenyl)-butylcarbamoyl)-methyl)-benzoic acid ([(18)F]repaglinide), a derivative of the sulfonylurea-receptor (SUR) ligand repaglinide, was synthesized as a potential tracer for the non-invasive investigation of the sulfonylurea 1 receptor status of pancreatic beta-cells by positron emission tomography (PET) in the context of type 1 and type 2 diabetes. [(18)F]Repaglinide could be obtained in an overall radiochemical yield (RCY) of 20% after 135 min with a radiochemical purity higher than 98% applying the secondary labeling precursor 2-[(18)F]fluoroethyltosylate. Specific activity w…