The Experts below are selected from a list of 213 Experts worldwide ranked by ideXlab platform
Shoichi Shimada - One of the best experts on this subject based on the ideXlab platform.
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Evans Blue is a specific antagonist of the human epithelial na channel δ subunit
Journal of Pharmacology and Experimental Therapeutics, 2005Co-Authors: Hisao Yamamura, Shinya Ugawa, Takashi Ueda, Shoichi ShimadaAbstract:The epithelial Na+ channel (ENaC) regulates Na+ homeostasis in cells and across epithelia. Four homologous ENaC subunits (α, β, γ, and δ) have been isolated in mammals. Combination of α-, β-, and γ-subunits or δ-, β-, and γ-subunits forms fully functional channels. Amiloride is a well known blocker of the ENaC family that inhibits both channel complexes. However, no specific antagonists are currently known that distinguish them. Here, we show that Evans Blue, a diagnostic aid for the measurement of blood volume and vascular permeability, inhibits the activity of the δ-subunit expressed in Xenopus oocytes. The inward currents at a holding potential of -60 mV in human ENaCδβγ-expressing oocytes were inhibited by the application of Evans Blue in a concentration-dependent manner with an IC50 value of 143 μM. Evans Blue markedly inhibited the δ-subunit current but did not block the α-subunit current. In conclusion, Evans Blue is the first known δ-subunit-specific antagonist of ENaC. This finding provides us with a key compound for elucidating the physiological and pathological functions of ENaCδ in humans and for drug development in the ENaC family.
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Evans Blue Is a Specific Antagonist of the Human Epithelial Na+ Channel δ-Subunit
The Journal of pharmacology and experimental therapeutics, 2005Co-Authors: Hisao Yamamura, Shinya Ugawa, Takashi Ueda, Shoichi ShimadaAbstract:The epithelial Na+ channel (ENaC) regulates Na+ homeostasis in cells and across epithelia. Four homologous ENaC subunits (α, β, γ, and δ) have been isolated in mammals. Combination of α-, β-, and γ-subunits or δ-, β-, and γ-subunits forms fully functional channels. Amiloride is a well known blocker of the ENaC family that inhibits both channel complexes. However, no specific antagonists are currently known that distinguish them. Here, we show that Evans Blue, a diagnostic aid for the measurement of blood volume and vascular permeability, inhibits the activity of the δ-subunit expressed in Xenopus oocytes. The inward currents at a holding potential of -60 mV in human ENaCδβγ-expressing oocytes were inhibited by the application of Evans Blue in a concentration-dependent manner with an IC50 value of 143 μM. Evans Blue markedly inhibited the δ-subunit current but did not block the α-subunit current. In conclusion, Evans Blue is the first known δ-subunit-specific antagonist of ENaC. This finding provides us with a key compound for elucidating the physiological and pathological functions of ENaCδ in humans and for drug development in the ENaC family.
Hisao Yamamura - One of the best experts on this subject based on the ideXlab platform.
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Evans Blue is a specific antagonist of the human epithelial na channel δ subunit
Journal of Pharmacology and Experimental Therapeutics, 2005Co-Authors: Hisao Yamamura, Shinya Ugawa, Takashi Ueda, Shoichi ShimadaAbstract:The epithelial Na+ channel (ENaC) regulates Na+ homeostasis in cells and across epithelia. Four homologous ENaC subunits (α, β, γ, and δ) have been isolated in mammals. Combination of α-, β-, and γ-subunits or δ-, β-, and γ-subunits forms fully functional channels. Amiloride is a well known blocker of the ENaC family that inhibits both channel complexes. However, no specific antagonists are currently known that distinguish them. Here, we show that Evans Blue, a diagnostic aid for the measurement of blood volume and vascular permeability, inhibits the activity of the δ-subunit expressed in Xenopus oocytes. The inward currents at a holding potential of -60 mV in human ENaCδβγ-expressing oocytes were inhibited by the application of Evans Blue in a concentration-dependent manner with an IC50 value of 143 μM. Evans Blue markedly inhibited the δ-subunit current but did not block the α-subunit current. In conclusion, Evans Blue is the first known δ-subunit-specific antagonist of ENaC. This finding provides us with a key compound for elucidating the physiological and pathological functions of ENaCδ in humans and for drug development in the ENaC family.
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Evans Blue Is a Specific Antagonist of the Human Epithelial Na+ Channel δ-Subunit
The Journal of pharmacology and experimental therapeutics, 2005Co-Authors: Hisao Yamamura, Shinya Ugawa, Takashi Ueda, Shoichi ShimadaAbstract:The epithelial Na+ channel (ENaC) regulates Na+ homeostasis in cells and across epithelia. Four homologous ENaC subunits (α, β, γ, and δ) have been isolated in mammals. Combination of α-, β-, and γ-subunits or δ-, β-, and γ-subunits forms fully functional channels. Amiloride is a well known blocker of the ENaC family that inhibits both channel complexes. However, no specific antagonists are currently known that distinguish them. Here, we show that Evans Blue, a diagnostic aid for the measurement of blood volume and vascular permeability, inhibits the activity of the δ-subunit expressed in Xenopus oocytes. The inward currents at a holding potential of -60 mV in human ENaCδβγ-expressing oocytes were inhibited by the application of Evans Blue in a concentration-dependent manner with an IC50 value of 143 μM. Evans Blue markedly inhibited the δ-subunit current but did not block the α-subunit current. In conclusion, Evans Blue is the first known δ-subunit-specific antagonist of ENaC. This finding provides us with a key compound for elucidating the physiological and pathological functions of ENaCδ in humans and for drug development in the ENaC family.
Klaus Starke - One of the best experts on this subject based on the ideXlab platform.
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Functional consequences of inhibition of nucleotide breakdown in rat vas deferens: a study with Evans Blue.
Naunyn-Schmiedeberg's archives of pharmacology, 1995Co-Authors: Ralph Bültmann, Bernd Driessen, Jorge Gonçalves, Klaus StarkeAbstract:The effect of Evans Blue on nucleotide breakdown, nucleotide-evoked contractions and electrically evoked contractions, overflow of ATP and overflow of tritium (after labelling with [3H]-noradrenaline) was studied in rat vas deferens. Pieces of vas deferens degraded 83 to 85% of added ATP, ADP and 2-methylthio ATP (all 100 μM) over 30 min. Evans Blue (100 μM) reduced this degradation to 22 to 26%. Nucleotides elicited contraction with potency declining in the order α, \-methylene ATP > 2-methylthio ATP > ATP > ADP. Evans Blue (100 μM) shifted the concentration-response curve of α, \-methylene ATP to the right and increased the maximum. Concentration-response curves of ATP, ADP and 2-methylthio ATP, in contrast, were shifted to the left and responses were much potentiated. In the presence of Evans Blue, the rank order of potency was ATP > 2-methylthio ATP > α, \-methylene ATP > ADP. Electrical field stimulation (100 pulses at 10 Hz) elicited contraction and an overflow of tritium and ATP. Evans Blue (100 μM) did not alter the contraction and the evoked overflow of tritium but increased 24-fold the evoked overflow of ATP. The results indicate that Evans Blue may serve as an — albeit impure — ecto-nucleotidase inhibitor in functional experiments. Such experiments demonstrate that the low potency of ATP (and also ADP and 2-methylthio ATP) in eliciting contraction, and the small size of the overflow of ATP upon sympathetic nerve stimulation, are due to rapid breakdown.
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Evans Blue blocks P2X-purinoceptors in rat vas deferens.
Naunyn-Schmiedeberg's archives of pharmacology, 1993Co-Authors: Ralph Bültmann, Klaus StarkeAbstract:In rat vas deferens, Evans Blue 100 μM increased contractions elicited by high K+ and by noradrenaline but markedly reduced contractions elicited by the P2X-purinoceptor-selective agonist α,β-methylene ATP (3 μM). The concentration-response curve of α,β-methylene ATP was shifted to the right by Evans Blue 30 μM and the maximal contraction was increased. In tissues incubated with nifedipine 10 μM, Evans Blue 100 μM tended to increase the residual contraction elicited by noradrenaline and abolished the residual response to α,β-methylene ATP (3 μM). The concentration-response curve of α,β-methylene ATP was progressively shifted to the right by increasing concentrations of Evans Blue in the presence of nifedipine; maximal contractions were increased by Evans Blue 10 and 30 but not 100 μM. From the shifts to the right caused by Evans Blue 30 μM, apparent pKB values of 5.9 (no nifedipine) and 6.0 (nifedipine present) were calculated. It is concluded that Evans Blue blocks P2X-purinoceptors in rat vas deferens and in addition causes a non-receptor-specific enhancement of contractions.
G.t. Gillies - One of the best experts on this subject based on the ideXlab platform.
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Determination of intracranial tumor volumes in a rodent brain using magnetic resonance imaging, Evans Blue, and histology: a comparative study
IEEE Transactions on Biomedical Engineering, 2000Co-Authors: S.s. Prabhu, W.c. Broaddus, C. Oveissi, S.s. Berr, G.t. GilliesAbstract:The measurement of tumor volumes is a practical and objective method of assessing the efficacy of a therapeutic agent. However, the relative accuracy of different methods of assessing tumor volume has been unclear. Using T/sub 1/-weighted, gadolinium-enhanced magnetic resonance imaging (T/sub 1/-MRI), Evans Blue infusion and histology the authors measured intracranial tumor volumes in a rodent brain tumor model (RT2) at days 10, 16 and 18 after implantation of cells in the caudate putamen. There is a good correlation between tumor volumes comparing T/sub 1/-MRI and Evans Blue (r/sup 2/=0.99), T/sub 1/-MRI and histology (r/sup 2/=0.98) and histology and Evans Blue (r/sup 2/=0.93). Each of these methods is reliable in estimating tumor volumes in laboratory animals. There was significant uptake of gadolinium and Evans Blue in the tumor suggesting a wide disruption of the blood-brain barrier.
Cy A. Stein - One of the best experts on this subject based on the ideXlab platform.
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Effect of Evans Blue and trypan Blue on syncytia formation and infectivity of human immunodeficiency virus type I and type II in vitro.
AIDS research and human retroviruses, 1991Co-Authors: Ranajit Pal, S. Mumbauer, George M. Hoke, Renato V. Larocca, Charles E. Myers, M. G. Sarngadharan, Cy A. SteinAbstract:Polyanionic compounds were used to inhibit infectivity of human immunodeficiency virus in vitro. Suramin, Evans Blue, and Trypan Blue were shown to inhibit syncytia formation normally observed when HIV-1-infected cells are cocultured with CD4+ cells. The inhibition was more pronounced with Evans Blue than with any of the other polyanions studied. The inhibitory effect was significantly weaker in HIV-2 systems. However, the reverse transcriptase activities of both types of viruses were inhibited by Evans Blue. Another polyanionic compound, phosphorothioate 28-mer cytidine homopolymer (SdC28) was shown to inhibit syncytium formation induced by HIV-1-and HIV-2-infected cells in an identical manner. Evans Blue showed partial blocking of gp120 binding to CD4 in a solid-phase enzyme-linked immunosorbent assay (ELISA). These results suggest that the polyanionic dyes may exert their antiviral effects, at least in part, by interfering with the binding and fusion of HIV with susceptible T cells.
