Search results for "Efflux"
showing 10 items of 106 documents
Intracellular pH-dependent efflux of the fluorescent probe pyranine in the yeast Yarrowia lipolytica.
2001
International audience; 8-Hydroxypyrene-1,3,6-trisulfonic acid (pyranine) can be used as a vital intracellular pH (pH(i)) indicator. In the yeast Yarrowia lipolytica, a partial efflux of the probe was detected by using the pH-independent wavelength of 415 nm. A simplified correction of the fluorescent signals was applied, enabling to show for this species a good near-neutral pH(i) maintenance capacity in a pH 3.9 medium. Octanoic acid, which is known to have toxic effects on yeast, decreased the pH(i) and increased the 260-nm-absorbing compounds leakage. However, this acid inhibited the fluorescent probe efflux linearly with its concentration suggesting a pH(i)-dependent efflux of pyranine …
Coincident glutamatergic depolarizations enhance GABAA receptor-dependent Cl- influx in mature and suppress Cl- efflux in immature neurons.
2021
The impact of GABAergic transmission on neuronal excitability depends on the Cl--gradient across membranes. However, the Cl--fluxes through GABAA receptors alter the intracellular Cl- concentration ([Cl-]i) and in turn attenuate GABAergic responses, a process termed ionic plasticity. Recently it has been shown that coincident glutamatergic inputs significantly affect ionic plasticity. Yet how the [Cl-]i changes depend on the properties of glutamatergic inputs and their spatiotemporal relation to GABAergic stimuli is unknown. To investigate this issue, we used compartmental biophysical models of Cl- dynamics simulating either a simple ball-and-stick topology or a reconstructed CA3 neuron. Th…
Studies on a new potential dopaminergic agent: in vitro BBB permeability, in vivo behavioural effects and molecular docking evaluation.
2015
2-Amino-N-[2-(3,4-dihydroxy-phenyl)-ethyl]-3-phenyl-propionamide (DA-PHEN) has been previously synthesized to obtain a potential prodrug capable of release dopamine (DA) into CNS. However, DA-PHEN could act per se as a dopaminergic drug. In this study, the permeability transport (Pe), obtained by parallel artificial permeability assay (PAMPA), indicated a low passive transcellular transport (Pe = 0.32 ± 0.01 × 10(-6 )cm/s). Using the Caco-2 cell system, the Papp AP-BL in absorptive direction (3.36 ± 0.02 × 10(-5 )cm/s) was significantly higher than the Papp BL-AP in secretive direction (1.75 ± 0.07 × 10(-5 )cm/s), suggesting a polarized transport. The efflux ratio (Papp AP-BL/Papp BL-AP = 0…
Intestinal drug efflux: formulation and food effects
2001
The intestine, primarily regarded as an absorptive organ, is also prepared for the elimination of certain organic acids, bases and neutral compounds depending on their affinity to intestinal carrier systems. Several of the transport systems known to mediate efflux in the major clearing organs--liver and kidney--are also expressed in the intestine. Examples of secretory transporters in the intestine are P-glycoprotein, members of the multidrug resistance associated protein family, breast cancer resistance protein, organic cation transporters and members of the organic anion polypeptide family. In this communication, the P-glycoprotein mediated intestinal secretion of talinolol, a model compo…
Utilizing inherent fluorescence of therapeutics to analyze real-time uptake and multi-parametric effector kinetics.
2011
Abstract The precise detection of pharmaceutical drug uptake and knowledge of a drug’s efficacy at the single-cell level is crucial for understanding a compound’s performance. Many pharmaceutical drugs, like the model substances Doxorubicin, Mitoxantrone or Irinotecan, have a distinctive natural fluorescence that can be readily exploited for research purposes. Utilizing this respective natural fluorescence, we propose a method analyzing simultaneously in real-time the efficiency, effects and the associated kinetics of compound-uptake and efflux in mammalian cells by flow cytometry. We show that real-time flow cytometric quantification of compound-uptake is reliably measured and that analyzi…
Verapamil Inhibits the Respiration Rate of Cancer Cells
1986
Calcium antagonists have successfully been used in the treatment of hypertension, cardiac arrhythmias and coronary heart disease. Recent evidence has suggested that such agents may also play a role in the treatment of malignant tumors. Verapamil, a calcium entry blocker, has been reported to enhance the cytotoxicity of several anticancer drugs under in vitro- and in vivo-conditions [1–10]. The effects observed could be explained by an enhanced drug accumulation due to a Verapamil-induced inhibition of the drug efflux from the cancer cells.
Relevance of Multidrug Resistance Proteins on the Clinical Efficacy of Cancer Therapy
2005
Variations in drug uptake and efflux, as well as changes in intracellular drug entrapment and distribution may represent important resistance mechanisms to cancer therapy. A variety of ATP binding cassette transporters (ABC) localised in multiple cell membranes is implied in those phenomena, representing a mechanism of protection of cells against xenobiotics. Many cancer cell lines over express some ABC transporters, especially p-glycoprotein, MRP1 and BCRP. This over expression is related to worse cancer treatment outcome and, in some cases, reduced overall survival of cancer patients. This paper reviews the location and physiological role of the three transporters mentioned and also descr…
Mechanism of the Citrate Transporters in Carbohydrate and Citrate Cometabolism in Lactococcus and Leuconostoc Species
1998
ABSTRACT Citrate metabolism in the lactic acid bacterium Leuconostoc mesenteroides generates an electrochemical proton gradient across the membrane by a secondary mechanism (C. Marty-Teysset, C. Posthuma, J. S. Lolkema, P. Schmitt, C. Divies, and W. N. Konings, J. Bacteriol. 178:2178–2185, 1996). Reports on the energetics of citrate metabolism in the related organism Lactococcus lactis are contradictory, and this study was performed to clarify this issue. Cloning of the membrane potential-generating citrate transporter (CitP) of Leuconostoc mesenteroides revealed an amino acid sequence that is almost identical to the known sequence of the CitP of Lactococcus lactis . The cloned gene was exp…
Choline Fluxes to and from the Rat Cerebral Cortex Studied with the “Cup Technique” in Vivo
1986
Since MacIntosh and Oborin (11) and later Mitchell (12) introduced the “cup technique” as a mean to study acetylcholine release from the cerebral cortex in vivo, this technique has been widely used for investigating the release of various neurotransmitters in anaesthetized as well as unanaesthetized mammals (2, 13, 14). Recently we proposed the “cup technique” as a way for studying the efflux of endogenous choline (Ch) from the rat cerebral cortex (4, 5) and to estimate changes in the extracellular concentration of Ch, if we consider the fluid filling the cup as an extension of the extracellular space.
Mind the gap—deficits in our knowledge of aspects impacting the bioavailability of phytochemicals and their metabolites—a position paper focusing on …
2015
This is an open access article under the terms of the Creative Commons Attribution-Non-Commercial-NoDerivs Licence.-- et al.