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1

Thymol, a constituent of thyme essential oil, is a positive allosteric modulator of human GABAA receptors and a homo-oligomeric GABA receptor from Drosophila melanogaster  

UK PubMed Central (United Kingdom)

The GABA-modulating and GABA-mimetic activities of the monoterpenoid thymol were explored on human GABAA and Drosophila melanogaster...Full Text Available

2003-12-01

2

Factors affecting actions of ethanol on GABA-activated chloride channels  

International Nuclear Information System (INIS)

Effects of ethanol in vitro on membrane vesicles were evaluated by monitoring "3"6Cl"- influx. Different assay parameters were tested to determine increased or decreased action of ethanol on GABA-activated chloride channels. The ability of 30 mM ethanol to augment "3"6Cl"- flux was seen at 0 degree C, in the absence of GABA, and at 34 degree C in the presence of GABA, using two different assay procedures. Picrotoxin blocked the direct effects of ethanol suggesting GABA_a involvement. Endogenous GABA in the medium surrounding the microsacs was assayed at different temperatures both in the presence and absence of GABA and ethanol. The direct effect of ethanol did not appear to involve the action of endogenous GABA. In addition to temperature effects on the assay, time of membrane storage also influenced ethanol action. Microsacs stored on ice ...

3

Effects of cultivar and culture conditions on g-aminobutyric acid accumulation in germinated fava beans (Vicia faba L.)  

British Library Electronic Table of Contents (United Kingdom)

BACKGROUND: High levels of g-aminobutyric acid (GABA) accumulate in plant tissues under various stresses. GABA accumulation is also influenced by cultivar. This aim of this study was to select the most promising cultivar of fava bean for GABA accumulation and to optimise the culture conditions for GABA production in germinated fava beans by response surface methodology based on central composite design (CCD). RESULTS: GABA content and glutamate decarboxylase activity in germinated seeds of cultivar S2 were significantly higher than those in other cultivars (P < 0.05). A significant negative correlation (r = -0.765, P < 0.05) between germination percentage and 1000-kernel weight was observed. There was a linear relationship between GABA content and sprout length (R2 = 0.816). The regression...

2010-01-01

4

Genetic Modulation of GABA Levels in the Anterior Cingulate Cortex by GAD1 and COMT  

UK PubMed Central (United Kingdom)

γ-Aminobutyric acid (GABA)-ergic transmission is critical for normal cortical function and is likely abnormal in a variety of neuropsychiatric disorders. We tested the in...Full Text Available

2010-07-01

5

Temporal development of GABA agonist induced alterations in ultrastructure and GABA receptor expression in cultured cerebellar granule cells  

DEFF Research Database (Denmark)

The temporal development of the effect of THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol) on the ultrastructure composition and GABA receptor expression in cerebellar granule cells was investigated by quantitative electron microscopy (morphometric analysis) and GABA binding assays. It was found that the cytoplasmic density of smooth endoplasmic reticulum was decreased, while the cytoplasmic density of rough endoplasmic reticulum, Golgi apparatus, vesicles and coated vesicles was greatly enhanced after exposure of the cells to THIP (150 microM) for only 1 hr. In cerebellar granule cells exposed to THIP (150 microM) for 3 hr low affinity GABA receptors were induced. These findings show that the effect of THIP on the ultrastructure composition and GABA receptor expression in cultured cerebellar granule cells may be interrelated and moreover it is likely that the turn-over of GABA ...

1987-01-01

6

Kinetic Parameters of Efflux of Penicillins by the Multidrug Efflux Transporter AcrAB-TolC of Escherichia coli?  

UK PubMed Central (United Kingdom)

The multidrug efflux transporter AcrAB-TolC is known to pump out a diverse range of antibiotics, including β-lactams. However, the kinetic constants of the efflux process, needed for the quantitative...Full Text Available

2010-05-01

7

Membrane Efflux and Influx Modulate both Multidrug Resistance and Virulence of Klebsiella pneumoniae in a Caenorhabditis elegans Model?  

UK PubMed Central (United Kingdom)

Cross-resistance to cefoxitin (FOX), chloramphenicol (CMP), and quinolones (nalidixic acid [NAL]) related to a putative efflux system overexpression has recently been reported for Klebsiella...Full Text Available

2010-10-01

8

Carrier-mediated Potassium Efflux Across the Cell Membrane of Red Beet  

UK PubMed Central (United Kingdom)

The flux ratio (influx/efflux) of K+ across the plasmalemma of beet cells at an external potassium concentration of 0.6 mm does not respond to changes of membrane potential in the...Full Text Available

1969-04-01

9

Aminoglycoside Efflux in Pseudomonas aeruginosa: Involvement of Novel Outer Membrane Proteins  

UK PubMed Central (United Kingdom)

The expression of tripartite multidrug efflux pumps such as MexA-MexB-OprM in Pseudomonas aeruginosa contributes to intrinsic resistance to a wide variety of antimicrobials, including...Full Text Available

2003-03-01

10

Zero net flux estimates of septal extracellular glucose levels and the effects of glucose on septal extracellular GABA levels  

UK PubMed Central (United Kingdom)

Although hippocampal infusions of glucose enhance memory, we have found repeatedly that septal glucose infusions impair memory when γ-aminobutyric acid (GABA) receptors are activated....Full Text Available

2009-06-02

11

Neuroactive steroids have multiple actions to potentiate GABAA receptors  

UK PubMed Central (United Kingdom)

The effects of neuroactive steroids on the function of GABAA receptors were studied using cell-attached records of single channel activity recorded from HEK293 cells transfected with α1...Full Text Available

2004-07-01

12

Calibration and analysis of soil carbon efflux estimates with closed chambers at Forsmark and Laxemar  

International Nuclear Information System (INIS)

The Forsmark and the Laxemar investigation areas are examined by the Swedish Nuclear Fuel and Waste Management Co. for a possible construction of a deep repository for nuclear waste. In the case of a future leakage of waste, the radioactive isotopes could end up in the ecosystems above the repository. The fate of the radionuclides and their possible radiological impacts are then highly determined by ecosystem carbon cycling. An important part of the carbon cycling is the soil carbon effluxes, and in the investigation areas soil carbon effluxes have been examined with the closed chamber technique. This paper is divided into two parts. Firstly, there were problems with the equipment measuring the soil carbon dioxide efflux, and the first part is a description of the problem, how it was corrected and its possible causes. The second part is a manual in how to analyse data and calculate annual estimates of soil carbon ...

2007-01-01

13

Beyond Acid Suppression: New Pharmacologic Approaches for Treatment of GERD  

British Library Electronic Table of Contents (United Kingdom)

Proton pump inhibitors are highly successful in treating gastroesophageal reflux disease, but a significant proportion of patients have persistent symptoms from weakly or nonacidic reflux. Transient lower esophageal sphincter relaxation (TLESR) represents the dominant mechanism of gastroesophageal reflux and has therefore become the most intensely investigated therapeutic target. The triggering of TLESR involve the vagal pathways and the ?-aminobutyric type B (GABA(B)) and metabotropic glutamate type 5 (mGluR5) receptors. Baclofen is a GABA(B) receptor agonist that is effective in inhibiting TLESR and reducing the number of reflux episodes, but is associated with significant central nervous system (CNS) side effects. The newer GABA(B) agonists, such as AZD9343 and AZD3355, and mGluR5 antag...

2010-01-01

14

Turgor-regulated sugar release in sugarbeet leaves  

Energy Technology Data Exchange (ETDEWEB)

Under drought conditions, sucrose distribution (osmotic adjustment vs. export) may be regulated at the mesophyll plasmalemma/tonoplast. Leaves were given {sup 14}CO{sub 2} for a 30/30 min pulse/chase. Peeled leaf discs were put in low or high osmotic solutions to monitor release of labeled solutes. High turgor increased efflux rates double those at low turgor. About 30% and 55% of the released label was in the sugar (sucrose + hexose) fractions at low and high turgor, respectively. Response to changes in cell turgor was rapid and reversible. PCMBS had no effect on efflux. NEM and CCCP enhanced efflux at high turgor. Presence of unlabeled sucrose in the wash solutions greatly enhanced sucrose efflux in a turgor-dependent manner; suggesting the presence of a sucrose exchange system, which appeared to be at the tonoplast. Turgor-regulated efflux involved both the tonoplast and ...

1989-04-01

15

Calmodulin Kinase II Interacts with the Dopamine Transporter C Terminus to Regulate Amphetamine-Induced Reverse Transport  

DEFF Research Database (Denmark)

Efflux of dopamine through the dopamine transporter (DAT) is critical for the psychostimulatory properties of amphetamines, but the underlying mechanism is unclear. Here we show that Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) plays a key role in this efflux. CaMKIIalpha bound to the distal C terminus of DAT and colocalized with DAT in dopaminergic neurons. CaMKIIalpha stimulated dopamine efflux via DAT in response to amphetamine in heterologous cells and in dopaminergic neurons. CaMKIIalpha phosphorylated serines in the distal N terminus of DAT in vitro, and mutation of these serines eliminated the stimulatory effects of CaMKIIalpha. A mutation of the DAT C terminus impairing CaMKIIalpha binding also impaired amphetamine-induced dopamine efflux. An in vivo role for CaMKII was supported by chronoamperometry measurements showing reduced amphetamine-induced dopamine efflux ...

2006-01-01

16

Selective Excitatory Actions of DNQX and CNQX in Rat Thalamic Neurons  

UK PubMed Central (United Kingdom)

The thalamic reticular nucleus (TRN) consists of GABA-containing neurons that form reciprocal synaptic connections with thalamic relay nuclei. Excitatory synaptic innervation of TRN neurons arises from...Full Text Available

2010-04-01

17

New insights into purinergic receptor signaling in neuronal differentiation, neuroprotection, and brain disorders  

UK PubMed Central (United Kingdom)

Ionotropic P2X and metabotropic P2Y purinergic receptors are expressed in the central nervous system and participate in the synaptic process particularly associated with acetylcholine, GABA, and glutamate...Full Text Available

2007-09-01

18

Long-term synaptic transformation of hippocampal CA1 gamma-aminobutyric acid synapses and the effect of anandamide.  

UK PubMed Central (United Kingdom)

Evidence is presented for a distinctive type of hippocampal synaptic modification [previously described for a molluscan gamma-aminobutyric acid (GABA) synapse after paired pre- and postsynaptic excitation]:...Full Text Available

1995-10-24

19

Cerebrospinal fluid zinc concentrations in febrile convulsions.  

UK PubMed Central (United Kingdom)

Zinc modulates the activity of glutamic acid decarboxylase, the rate limiting enzyme in the synthesis of gamma-aminobutyric acid (GABA), which is a major inhibitory neurotransmitter. Low cerebrospinal...Full Text Available

1995-10-01

20

Practical applications and feasibility of efflux pump inhibitors in the clinic-A vision for applied use  

British Library Electronic Table of Contents (United Kingdom)

The world of antibiotic drug discovery and development is driven by the necessity to overcome antibiotic resistance in common Gram-positive and Gram-negative pathogens. However, the lack of Gram-negative activity among both recently approved antibiotics and compounds in the developmental pipeline is a general trend despite the fact that the plethora of covered drug targets are well-conserved across the bacterial kingdom. Such intrinsic resistance in Gram-negative bacteria is largely attributed to the activity of multidrug resistance (MDR) efflux pumps. Moreover, these pumps also play a significant role in acquired clinical resistance. Together, these considerations make efflux pumps attractive targets for inhibition in that the resultant efflux pump inhibitor (EPI)/antibiotic combination d...

2006-01-01

 
 
 
 
21

The effect of ethanol on "3"5-S-TBPS binding to mouse brain membranes in the presence of chloride  

International Nuclear Information System (INIS)

The effect of in vitro and in vivo administration of ethanol on the binding of "3"5S-t-butyl-bicyclophosphorothionate ("3"5S-TBPS) to cortical brain membranes of C57B1 mice was investigated using KCl (100 mM) containing assay media. The in vitro addition of ethanol produced a dose-dependent inhibition of basal "3"5S-TBPS binding. In the presence of chloride ions, GABA and pentobarbital had a biphasic action (stimulation followed by inhibition) on "3"5S-TBPS binding, whereas diazepam only stimulated the binding. Ethanol reduced the stimulatory effects of GABA and pentobarbital in a dose-dependent manner, but had no effect on the enhancement of "3"5S-TBPS binding produced by diazepam. "3"5S-TBPS binding to cortical brain membranes was inhibited by the putative Cl"- channel blocking agent DIDS. This inhibitory action of DIDS was significantly, and dose-dependently reduced by ethanol (#<=# 100 mM ethanol). Chronic ethanol ingestion in vivo, ...

22

The efflux of a fluorescent probe is catalyzed by an ATP-driven extrusion system in Lactococcus lactis.  

UK PubMed Central (United Kingdom)

Many bacteria, both gram positive and gram negative, extrude in an energy-dependent manner the fluorescent pH indicator 2',7'-bis-(2-carboxyethyl)-5[and -6]-carboxyfluorescein (BCECF) (D. Molenaar,...Full Text Available

1992-05-01

23

Sugar Efflux from Maize (Zea mays L.) Pedicel Tissue 1  

UK PubMed Central (United Kingdom)

Sugar release from the pedicel tissue of maize (Zea mays L.) kernels was studied by removing the distal portion of the kernel and the lower endosperm, followed by replacement of the...Full Text Available

1985-03-01

24

Regulation and Function of Escherichia coli Sugar Efflux Transporter A (SetA) during Glucose-Phosphate Stress?  

UK PubMed Central (United Kingdom)

Accumulation of certain nonmetabolizable sugar-phosphates (including α-methyl glucoside-6-phosphate) in Escherichia coli is growth inhibitory and elicits the glucose-phosphate...Full Text Available

2011-01-01

25

Phytochrome-controlled Hydrogen Ion Excretion by Avena Coleoptiles 1  

UK PubMed Central (United Kingdom)

A red light-induced, far red reversible stimulation of proton efflux from apical segments of etiolated Avena sativa L. cv. Victory coleoptiles was observed. The acidification...Full Text Available

1977-04-01

26

Neurobehavioral effects of power-frequency electromagnetic fields.  

UK PubMed Central (United Kingdom)

Some laboratory experiments have suggested that power-frequency electric and magnetic fields (EMF) may be capable of influencing calcium efflux from cell membranes, pineal function, and circadian rhythms....Full Text Available

1993-12-01

27

Lack of Influence of Phytochrome on Membrane Permeability to Tritiated Water 1  

UK PubMed Central (United Kingdom)

The water permeability of tissues was investigated by measuring the efflux of 3HHO from previously loaded (in darkness) etiolated bean buds (Phaseolus vulgaris L. var. Red...Full Text Available

1976-02-01

28

Identification of the Haemophilus influenzae tolC Gene by Susceptibility Profiles of Insertionally Inactivated Efflux Pump Mutants  

UK PubMed Central (United Kingdom)

Isogenic strains containing insertional disruptions of 10 Haemophilus influenzae Rd genes were investigated for their effects on the susceptibility of the organism to various classes...Full Text Available

2004-04-01

29

Differential chemosensitization of P-glycoprotein overexpressing K562/Adr cells by withaferin A and Siamois polyphenols  

UK PubMed Central (United Kingdom)

BackgroundMultidrug resistance (MDR) is a major obstacle in cancer treatment and is often the result of overexpression of the drug efflux protein, P-glycoprotein (P-gp), as a consequence...Full Text Available

30

Calcium Effects on Stomatal Movement in Commelina communis L. 1  

UK PubMed Central (United Kingdom)

Stomatal movements depend on both ion influx and efflux; attainment of steady state apertures reflects modulation of either or both processes. The role of Ca2+ in those two processes was...Full Text Available

1988-07-01

31

Boron Tolerance in Barley Is Mediated by Efflux of Boron from the Roots1  

UK PubMed Central (United Kingdom)

Many plants are known to reduce the toxic effects of high soil boron (B) by reducing uptake of B, but no mechanism for limiting uptake has previously been identified. The B-tolerant cultivar of barley...Full Text Available

2004-10-01

32

Triphenylmethylphosphonium cation distribution as a measure of hormone-induced alterations in white adipocyte membrane potential  

Energy Technology Data Exchange (ETDEWEB)

Triphenylmethylphosphonium (TPMP+) partitions into the mitochondrial and cytosolic compartments in the rat white adipocyte in a potential-dependent fashion. The relationship between (/sup 3/H)TPMP+ distribution, intracellular cAMP generation and lipolysis in response to hormones and cAMP-mimetic compounds was examined. Half-maximal (/sup 3/H)TPMP+ efflux and glycerol release were produced by 15 and 9 nM adrenocorticotropin, 170 and 110 nM 1-epinephrine, 70 and 27 microM isobutylmethylxanthine and 800 and 750 microM dibutyryl cAMP, respectively. Hormone-stimulated cAMP generation was also correlated with (/sup 3/H)TPMP+ efflux and lipolysis in terms of concentration dependency. In kinetic experiments, glycerol release and (/sup 3/H)TPMP+ efflux in response to adrenocorticotropin or cholera toxin proceeded over a similar time course, whereas an earlier rise in cAMP generation was detected. The depolarizing effect of lipolytic ...

1982-01-01

33

Extracellular ATP4- promotes cation fluxes in the J774 mouse macrophage cell line  

Energy Technology Data Exchange (ETDEWEB)

Extracellular ATP stimulates transmembrane ion fluxes in the mouse macrophage cell line J774. In the presence of Mg2+, nonhydrolyzable ATP analogs and other purine and pyrimidine nucleotides do not elicit this response, suggesting the presence of a specific receptor for ATP on the macrophage plasma membrane. One candidate for such a receptor is the ecto-ATPase expressed on these cells. We, therefore, investigated the role of this enzyme in ATP-induced /sup 86/Rb+ efflux in J774 cells. The ecto-ATPase had a broad nucleotide specificity and did not hydrolyze extracellular ATP in the absence of divalent cations. /sup 86/Rb+ efflux was not blocked by inhibition of the ecto-ATPase and did not require Ca2+ or Mg2+. In fact, ATP-stimulated /sup 86/Rb+ efflux was inhibited by Mg2+ and correlated with the availability of ATP4- in the medium. In the absence of divalent cations, the slowly hydrolyzable ATP analogs adenosine ...

1987-03-05

34

Blockade of androgen receptors is sufficient to alter the sexual differentiation of the substantia nigra pars reticulata seizure-controlling network  

UK PubMed Central (United Kingdom)

The substantia nigra pars reticulata (SNR) controls seizures in a sex-specific manner. At postnatal day 15 (P15), SNR infusion of GABAA receptor agonist muscimol have proconvulsant...Full Text Available

2008-03-01

35

Altered GABAA receptor-mediated synaptic transmission disrupts the firing of gonadotropin-releasing hormone neurons in male mice under conditions that mimic steroid abuse  

UK PubMed Central (United Kingdom)

Gonadotropin–releasing hormone (GnRH) neurons are the central regulators of reproduction. GABAergic transmission plays a critical role in pubertal activation of pulsatile GnRH secretion....Full Text Available

2010-05-12

36

Protracted ethanol withdrawal in rats: Tolerance to the anxiolytic effects of diazepam and pentobarbital but not phenobarbital  

Science.gov (United States)

Anxiety is a common symptom during ethanol withdrawal contributing to its continuous abuse and alcoholism. Ethanol withdrawal in rats produces an interoceptive discriminative stimulus (IDS) similar to that produced by the anxiogenic drug pentylenetetrazol (PTZ). This stimulus peaks at 12 hours after last dose of ethanol and thereafter the IDS is detected for several days (protracted withdrawal) by sensitization to a probe drug. previously, the authors have shown that during the protracted withdrawal, the IDS is enhanced by GABA receptor antagonists suggesting alteration of brain GABA systems. This report provides further evidence that chronic ethanol alters GABAergic systems. Rats were trained to discriminate PTZ (20 mg/kg, ip) from saline. Diazepam, pentobarbital and phenobarbital blocked the PTZ-IDS dose dependently. Ethanol, 4.5% w/v, was then given in a nutritionally complete diet for a week. On termination of the ethanol diet, rats ...

1990-02-26

37

Sucrose accumulation in mature sweet melon fruits. [Cucumis melo  

Energy Technology Data Exchange (ETDEWEB)

Mesocarp tissue from sucrose-accumulating sweet melon (Cucumis melo cv. Galia) showed sucrose synthase activity (ca 1 nkat/gfw) while soluble acid invertase and sucrose phosphate synthase activities were not observed. Sucrose uptake into mesocarp discs was linear with sucrose concentration (1-500 mM) and unaffected by PCMBS and CCCP. Sucrose compartmentation into the vacuole also increased linearly with sucrose concentration as indicated by compartmental efflux kinetics. Mesocarp discs incubated in /sup 14/C-fructose + UDP-glu synthesized /sup 14/C-sucrose and efflux kinetics indicated that the /sup 14/C-sucrose was compartmentalized. These data support the hypothesis that two mechanisms are involved in sucrose accumulation in sweet melon: (1) compartmentation of intact sucrose and (2) synthesis of sucrose via sucrose synthase and subsequent compartmentation in the vacuole.

1987-04-01

38

New Plasmid-Mediated Fluoroquinolone Efflux Pump, QepA, Found in an Escherichia coli Clinical Isolate?  

UK PubMed Central (United Kingdom)

Plasmid-mediated Qnr and AAC(6′)-Ib-cr have been recognized as new molecular mechanisms affecting fluoroquinolone (FQ) resistance. C316, an Escherichia coli strain demonstrating...Full Text Available

2007-09-01

39

5'-Azido-[3,6-3H2]-1-napthylphthalamic acid, a photoactivatable probe for naphthylphthalamic acid receptor proteins from higher plants: identification of a 23-kDa protein from maize coleoptile plasma membranes.  

UK PubMed Central (United Kingdom)

1-Naphthylphthalamic acid (NPA) is a specific inhibitor of polar auxin transport that blocks carrier-mediated auxin efflux from plant cells. To allow identification of the NPA receptor thought to be...Full Text Available

1992-01-15

40

Study of epileptiform activity in cerebral ganglion of mud crab Scylla serrata  

British Library Electronic Table of Contents (United Kingdom)

An attempt is made to induce in mud crab (Scylla serrata) epileptiform activities that resemble the generalized epileptic seizures. Cerebral ganglion of crab was exposed in situ, to a convulsant drug pentylenetetrazole (PTZ) 100?mM, for induction of seizures. Also, crabs were pretreated with antiepileptic drug viz sodium valproate (120??mol/l) to inhibit epileptiform activities. The surface electrical discharges of cerebral ganglion were recorded using Unkelscope (MIT, USA) in control as well as experimental animals. The cerebral ganglion of crab showed a pattern of high cerebral electrical discharges after PTZ treatment compared to control. The sodium valproate promoted sedative action in control and prevented PTZ-mediated epileptiform discharges. Glutamate and GABA contents in cerebral g...

2011-01-01

 
 
 
 
41

The multidrug resistance efflux complex, EmrAB from Escherichia coli forms a dimer in vitro  

International Nuclear Information System (INIS)

Tripartite efflux systems are responsible for the export of toxins across both the inner and outer membranes of Gram negative bacteria. Previous work has indicated that EmrAB-TolC from Escherichia coli is such a tripartite system, comprised of EmrB an MFS transporter, EmrA, a membrane fusion protein and TolC, an outer membrane channel. The whole complex is predicted to form a continuous channel allowing direct export from the cytoplasm to the exterior of the cell. Little is known, however, about the interactions between the individual components of this system. Reconstitution of EmrA + EmrB resulted in co-elution of the two proteins from a gel filtration column indicating formation of the EmrAB complex. Electron microscopic single particle analysis of the reconstituted EmrAB complex revealed the presence of particles approximately 240 x 140 A, likely to correspond to two EmrAB dimers in a back-to-back arrangement, suggesting the dimeric EmrAB form is the ...

2009-03-06

42

Interactions between the chemotherapeutic agent eribulin mesylate (E7389) and P-glycoprotein in CF-1 abcb1a-deficient mice and Caco-2 cells  

British Library Electronic Table of Contents (United Kingdom)

Eribulin is a new anticancer agent currently in Phase III clinical trials for the treatment of metastatic breast cancer. In the current studies, we have investigated the effects of P-glycoprotein (P-gp) on the in vivo disposition of eribulin using CF-1 abcb1a-deficient mice, and the influence of eribulin on P-gp-mediated efflux of digoxin in Caco-2 cells. Eribulin was administered intravenously and orally in both CF-1 wild-type and CF-1 abcb1a-deficient mice. P-gp-mediated efflux of digoxin in Caco-2 cell monolayers was measured in the presence of eribulin. The plasma exposure to eribulin was higher in CF-1 abcb1a-deficient mice than that in CF-1 wild-type mice after intravenous (IV) and oral (PO) administrations. The oral bioavailability of eribulin was 62.3% in CF-1 abcb1a-deficient mice...

2011-01-01

43

Interactions between organic anions on multiple transporters in Caco-2 cells.  

Science.gov (United States)

In drug development, Caco-2 cells are often employed to study the influence of membrane transporters on drug permeability. The aim of the current study was to characterize permeability and kinetic parameters of selected organic anionic compounds in Caco-2 cells, and to investigate whether the Caco-2 cell line may be used as an overall model to predict interactions on multiple membrane transporters in the intestine. Taurocholic acid (TCA) and estrone-3-sulfate (E(1) S) were used as model substrates. Possible inhibitors studied were TCA, E(1) S, taurolithocholic acid, fluvastatin, and glipizide. The effects of these compounds on initial uptake, apparent permeability, and intracellular end-point accumulations of the probe substrates were studied. Both interactions on apical and basolateral influx transporters were observed. These interactions were proposed to be mediated mainly by the apical sodium-dependent bile acid transporter and the organic solute transporter ?/?, and to less extent ...

2011-05-23

44

An arsenic metallochaperone for an arsenic detoxification pump  

Science.gov (United States)

Environmental arsenic is a world-wide health issue, making it imperative for us to understand mechanisms of metalloid uptake and detoxification. The predominant intracellular form is the highly mephitic arsenite, which is detoxified by removal from cytosol. What prevents arsenite toxicity as it diffuses through cytosol to efflux systems? Although intracellular copper is regulated by metallochaperones, no chaperones involved in conferring resistance to other metals have been identified. In this article, we report identification of an arsenic chaperone, ArsD, encoded by the arsRDABC operon of Escherichia coli. ArsD transfers trivalent metalloids to ArsA, the catalytic subunit of an As(III)/Sb(III) efflux pump. Interaction with ArsD increases the affinity of ArsA for arsenite, thus increasing its ATPase activity at lower concentrations of arsenite and enhancing the rate of arsenite extrusion. Cells are consequently resistant to environmental ...

2006-10-17

45

Mathematical model of absorption of carbon dioxide by rescur breathing apparatus scrubber  

Energy Technology Data Exchange (ETDEWEB)

The author presents a mathematical model for analysis of the impact of scrubber bed length, porosity, and gas flow rate on the absorption of CO{sub 2} in a breathing apparatus. The model accounts for the decrease in available absorbent through chemical conversion. The predicted efflux of CO{sub 2} from a canister containing LiOH compared favorably with measured values reported elsewhere. It was determined from a computational study that the time for breakthrough of CO{sub 2} at a prescribed level is nearly directly proportional to bed length and inversely proportional to gas flow and porosity.

1987-01-01

46

Experimental investigation of the length of a free diffusion jet of fuel gases diluted with inert gases  

Science.gov (United States)

Experimental investigation of the length of single burning jets of methane and hydrogen previously diluted with an inert gas (nitrogen or helium) was carried out. Efflux of fuel gases into the atmosphere occurred through cylindrical extension pieces 4 and 8 mm in diameter. The Reynolds numbers at the cut of a piece varied in the range from 400 to 12,000. A clearly defined dependence of the jet length on the quality of the added inert gas is obtained. The correlation of experimental data made it possible to recommend formulas for engineering calculations of free laminar and turbulent jets.

2010-05-01

47

Dipyrone-induced changes in DNA repair and other cell membrane associated processes in Escherichia coli  

Energy Technology Data Exchange (ETDEWEB)

The analgesic, dipyrone (1,phenyl-2,3-dimethyl-5-pyrazolone-4-methylamino methane sulphonate sodium), at 20 mM concentration, inhibited the rejoining of single-strand scissions in DNA of Escherichia coli B/r cells induced by 20 krad gamma-radiation. The chemical altered the cell membrane structure as evidenced from the uptake of acriflavin, the efflux of potassium ions from the bacterial cells and the inhibition of alkaline phosphatase-a cell membrane associated enzyme. (author). 18 refs., 6 figures.

1982-09-01

48

Dipyrone-induced changes in DNA repair and other cell membrane associated processes in Escherichia coli  

International Nuclear Information System (INIS)

The analgesic, dipyrone (1,phenyl-2,3-dimethyl-5-pyrazolone-4-methylamino methane sulphonate sodium), at 20 mM concentration, inhibited the rejoining of single-strand scissions in DNA of Escherichia coli B/r cells induced by 20 krad gamma-radiation. The chemical altered the cell membrane structure as evidenced from the uptake of acriflavin, the efflux of potassium ions from the bacterial cells and the inhibition of alkaline phosphatase-a cell membrane associated enzyme. (author).

49

Nerve growth factor actions on the brain  

International Nuclear Information System (INIS)

We examined the effect of the trophic protein, nerve growth factor (NGF), on cultures of fetal rat neostriatum and basal forebrain-medial septal area (BF-MS) to define its role in brain development. Treatment of cultures with NGF resulted in an increase in the specific activity of the cholinergic enzyme choline acetyltransferase (CAT) in both brain areas. CAT was immunocytochemically localized to neurons. In the BF-MS, NGF treatment elicited a marked increase in staining intensity and an apparent increase in the number of CAT-positive neurons. Moreover, treatment of BF-MS cultures with NGF increased the activity of acetylcholinesterase, suggesting that the cholinergic neuron as a whole was affected. To begin defining mechanisms of action of NGF in the BF-MS, we detected NGF receptors by two independent methods. Receptors were localized to two different cellular populations: neuron-like cells, and non-neuron-like cells. Dissociation studies with ["1"2"5I]NGF suggested that high affinity ...

50

Submitochondrial distribution of cAMP in its incubation with rat liver mitochondria  

Energy Technology Data Exchange (ETDEWEB)

When labeled cAMP is incubated with isolated mitochondria from rat liver, it penetrates not only through the outer membrane of the mitochondria but also into the mitoplasts, where it is accumulated chiefly in the matrix. Damage to the mitochondrial membrane by freezing-thawing promotes not an influx but an efflux of cAMP out of the mitoplasts. A substantial part of the labeled nucleotide in all the investigated submitochondrial fractions was identified as intact cAMP by the method of thin-layer chromatography. The transport of cAMP into the mitochondria can explain the activation of their functions by the hormones that activate cytoplasmic adenylate cyclase and by extramitochondrial (cytosol) cAMP, as well as the presence of cAMP-dependent protein kinase and cAMP-phosphodiesterase in the mitochondria.

1986-03-20

51

Intermediate-conductance calcium-activated potassium channels participate in neurovascular coupling  

British Library Electronic Table of Contents (United Kingdom)

BACKGROUND AND PURPOSE Controlling vascular tone involves K+ efflux through endothelial cell small- and intermediate-conductance calcium-activated potassium channels (KCa2.3 and KCa3.1, respectively). We investigated the expression of these channels in astrocytes and the possibility that, by a similar mechanism, they might contribute to neurovascular coupling. EXPERIMENTAL APPROACH Transgenic mice expressing enhanced green fluorescent protein (eGFP) in astrocytes were used to assess KCa2.3 and KCa3.1 expression by immunohistochemistry and RT-PCR. KCa currents in eGFP-positive astrocytes were determined in situ using whole-cell patch clamp electrophysiology. The contribution of KCa3.1 to neurovascular coupling was investigated in pharmacological experiments using electrical field stimulatio...

2011-01-01

52

Effect of vanadate on proton-sucrose cotransport in Ricinus cotyledons  

Energy Technology Data Exchange (ETDEWEB)

The effects of orthovanadate on the uptake of sucrose by Ricinus cotyledons and on sucrose-coupled proton influx were measured in order to gain insight into the relationship to the plasma membrane proton pump. Vanadate had no effect on short-term sucrose uptake. In long-term experiments (> 30 min) sucrose uptake was progressively inhibited, but only at high external sucrose concentrations. Vanadate did not affect proton efflux pumping in the absence of sucrose and neither did it change the initial rate of sucrose-coupled proton influx. However, it enhanced the maximal level of sucrose-induced alkalization of the medium at all sucrose concentrations tested. This is interpreted as an inhibiting effect of vanadate on the proton pump that recycles protons during sucrose-proton cotransport. The sensitivity towards vanadate indicates that this proton pump is an ATPase. A second proton-translocating system, that is insensitive to vanadate, is postulated to function in ...

1987-07-01

53

Transcriptional Profiling Analysis of the Global Regulator NorG, a GntR-Like Protein of Staphylococcus aureus.  

Science.gov (United States)

The GntR-like protein NorG has been shown to affect Staphylococcus aureus genes involved in the resistance to quinolones and ?-lactams, such as those encoding the NorB and AbcA transporters. To identify the target genes regulated by NorG, we carried out transcriptional profiling assays using S. aureus RN6390 and its isogenic norG::cat mutant. Our data showed that NorG positively affected the transcription of global regulators mgrA, arlS, and sarZ. The three putative drug efflux pump genes most positively affected by NorG were the NorB efflux pump (5.1-fold), the MmpL-like protein SACOL2566 (5.2-fold), and the BcrA-like drug transporter SACOL2525 (5.7-fold). The S. aureus predicted MmpL protein showed 53% homology with the MmpL lipid transporter of Mycobacterium tuberculosis, and the putative SACOL2525 protein showed 87% homology with the bacitracin drug transporter BcrA of Staphylococcus hominis. Two pump genes most negatively affected by NorG ...

2011-09-01

54

Fluxes of H+ and K+ in corn roots  

International Nuclear Information System (INIS)

We report here on an experimental system that utilizes ion-selective microelectrodes to measure the electrochemical potential gradients for H"+ and K"+ ions within the unstirred layer near the root surface of both tact 4-day-old corn seedlings and corn root segments. Analysis of the steady state H"+ and K"+ electrochemical potential gradients provided a simultaneous measure of the fluxes crossing a localized region of the root surface. Net K"+ influx values obtained by this method were compared with unidirectional K"+ ("8"6Rb"+) influx kinetic data; at any particular K"+ concentration, similar values were obtained by either technique. The ion-specific microelectrode system was then used to investigate the association between net H"+ efflux and net K"+ influx. Although the computed H"+K"+ stoichiometry is dependent upon the choice of diffusion coefficients, the values obtained were extremely variable, and net K"+ influx rarely appeared to be charge-balanced by H"+ ...

1987-01-01

55

Cell volume regulation in hemoglobin CC and AA erythrocytes  

International Nuclear Information System (INIS)

Swelling hemoglobin CC erythrocytes stimulates a ouabain-insensitive K flux that restores original cell volume. Studies were performed with the K analog, "8"6Rb. This volume regulatory pathway was characterized for its anion dependence, sensitivity to loop diuretics, and requirement for Na. The swelling-induced K flux was eliminated if intracellular chloride was replaced by nitrate and both swelling-activated K influx and efflux were partially inhibited by 1 mM furosemide or bumetanide. K influx in swollen hemoglobin CC cells was not diminished when Na in the incubation medium was replaced with choline, indicating Na independence of the swelling-induced flux. Identical experiments with hemoglobin AA cells also demonstrated a swelling-induced increase in K flux, but the magnitude and duration of this increase were considerably less than that seen with hemoglobin CC cells. The increased K flux in hemoglobin AA cells was likewise sensitive to anion replacement and to ...

56

Action Potentials in a Giant Algal Cell: A Comparative Approach to Mechanisms and Evolution of Excitability  

Science.gov (United States)

The giant alga Chara corallina generates action potentials (APs) in response to mechanical stimulation, injury, or direct electrical stimulation. Students examine the waveform characteristics of these APs using standard intracellular recording techniques. Intracellular recording is easier than with neurons because of the large size of the Chara cell. Students observe very negative resting potentials (up to -250 mV), large AP amplitudes with depolarizing peaks approaching 0 mV, AP durations of seconds, and refractory periods up to several minutes. Students calculate Nernst potentials for the ions distributed across the Chara cell membrane to hypothesize the ions responsible for the resting potential and for the depolarizing phase of the AP. These calculations suggest that K+ is responsible for the resting potential and that Ca2+ influx and Ca2+-activated Cl- efflux are responsible for depolarizing phases of the AP, which they are. Comparison of the Chara AP ...

2008-06-11

57

Uptake, transport, and storage of calcium and magnesium in spruce (Picea abies [L]Karst.) and pine (Pinus silvestris L.) as affected by variable nutrition and pollutant stress  

International Nuclear Information System (INIS)

Statements about the dynamic processes of uptake, transport, and deposition of Ca and Mg in norway spruce and Scots pine are made in this paper. Concerning the storage of these elements it is shown that there are great differences in their functional importance in cell metabolism. There is evidence that the role of Mg in enzyme and protein metabolism is of far greater significance for the understanding of Mg-deficiency symptoms than its function as the central atom of the chlorophyll complexes. In regard to the transport and especially to the incorporation of Ca into the needles differences between species were evident, expressing the special status of pine among the gymnosperms. With increasing needle age an accumulation of Ca-oxalate crystals, which are physiologically inert, could be proved for the studied conifers. This was interpreted as a 'detoxication' from surplus Ca to hold constant the level of the physiologically active fraction. Accordingly, the low Ca-contents of yellowed ...

58

Contribution of calcium ions and hydrogen ions to the signal transduction chain in phytochrome-mediated spore germination. [Onoclea sensibilis L  

Energy Technology Data Exchange (ETDEWEB)

Red light stimulates germination in the spores of Onoclea sensibilis L. Phytochrome is confirmed to be the photoreceptor pigment in the germination response by demonstrating red-far-red photoreversibility. External Ca/sup 2 +/ is required for this response with a threshold at a submicromolar concentration. Red light stimulates an increase in the total concentration of intracellular calcium in the spores as determined by atomic absorption spectroscopy. Subsequent exposure to far-red light inhibits the red light-induced increase in intracellular calcium. The majority of the increase occurs 5 minutes after the onset of irradiation. The calcium-antagonist, La/sup 3 +/ inhibits both germination and the red light-induced increase in intracellular calcium. Using /sup 31/P-nuclear magnetic resonance spectroscopy, the author tested the hypothesis that a sustained increase in intracellular pH contributes to the signal transduction chain. He never detected a red light-induced increase in ...

1985-01-01

59

Biological effects of exogenous adenosine 5 prime -triphosphate on cultured mammalian cells: Evidence for a receptor mechanism and its regulation by desensitization  

Energy Technology Data Exchange (ETDEWEB)

Exogenous adenosine 5{prime}-triphosphate (ATP) mobilized intracellular calcium in human carcinoma A43l cells and in Swiss 3T3 and 3T6 mouse fibroblasts by increasing inositol trisphosphate similar to well down growth factors (platelet-derived growth factor (PDGF), epidermal growth factor (EGF), bradykinin (BK), serum). Calcium mobilization was examined by video imaging of fura-2 fluorescence is single cells, following the radioactive isotope {sup 45}Ca, and monitoring the decrease in fluorescence of cells loaded with chlortetracycline. Uridine 5{prime}-triphosphate, but not other nucleotides, mimicked ATP. Single-cell analysis revealed synchronous responses in 10 sec to ATP, BK or serum, while PDGF (3T3) and EGF (A431) produced slower signals with significant cell-to-cell variation. PDGF desensitized 3T3 cells to ATP and BK added 100 sec later but ATP or BK did not desensitized to PDGF. Homologous desensitization was seen with all agonists. Heterologous desensitization was also ...

1989-01-01

60

In vitro evaluation of herpes simplex virus type 1 thymidine kinase reporter system in dynamic studies of transcriptional gene regulation  

Energy Technology Data Exchange (ETDEWEB)

The herpes simplex virus type 1 thymidine kinase (HSV1-TK) reporter system is being used to directly and indirectly monitor therapeutic gene expression, immune cell trafficking and protein-protein interactions in various living animals. However, the issues of HSV1-TK enzyme stability in living cells and whether this reporter system is optimal for dynamic studies of gene expression events in genetic imaging have not be addressed. The purpose of the present study was to evaluate the application of this reporter system in dynamic studies of transcriptional gene regulation. To achieve this purpose, we established two tetracycline-inducible murine sarcoma cell lines, tetracycline-turn-off HSV1-tk-expressing cell line (NG4TL4/tet-off-HSV1-tk) and tetracycline-turn-off Luc-expressing cell line (NG4TL4/tet-off-Luc), to create an artificially regulated gene expression model in vitro. The dynamic transcriptional events mediating a series of doxycycline (Dox) inductions were monitored by HSV1-TK ...

2006-07-15