Vanadium, Na-K-ATPase, and potassium adaptation in the rat

Vanadate is a potent inhibitor of Na-K-ATPase in vitro. It has been suggested that vanadium may function as a cellular regulator of Na-K-ATPase in vivo. To examine this speculation, we studied in rats the effect of high vanadate intake on 1) the tissue levels and distribution of vanadium, 2) basal activity of Na-K-ATPase in various tissues, and 3) the activity of Na-K-ATPase in various organs under conditions of massive chronic potassium loading known to stimulate Na-K-ATPase in the kidney and colon. Despite extremely high tissue levels of vanadium there was no demonstrable effect of the element on the basal activity of Na-K-ATPase. When subjected to chronic potassium loading, rats with high tissue vanadium concentrations underwent potassium adaptation that was associated with a rise in Na-K-ATPase activity in the renal cortex, renal medulla, and colonic mucosa. Further studies are needed to support or refute the thesis that vanadium might be an intracellular regulator of Na-K-ATPase in vivo.

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CHIR-124, a Novel Potent Inhibitor of Chk1, Potentiates the Cytotoxicity of Topoisomerase I Poisons In vitro and In vivo

Clinical Cancer Research ◽

10.1158/1078-0432.ccr-06-1424 ◽

2007 ◽

Vol 13 (2) ◽

pp. 591-602 ◽

Cited By ~ 99

Author(s):

Archie N. Tse ◽

Katherine G. Rendahl ◽

Tahir Sheikh ◽

Haider Cheema ◽

Kim Aardalen ◽

...

Keyword(s):

Topoisomerase I ◽

Potent Inhibitor

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A highly potent inhibitor of cathepsin K (relacatib) reduces biomarkers of bone resorption both in vitro and in an acute model of elevated bone turnover in vivo in monkeys

Bone ◽

10.1016/j.bone.2006.07.015 ◽

2007 ◽

Vol 40 (1) ◽

pp. 122-131 ◽

Cited By ~ 95

Author(s):

S. Kumar ◽

L. Dare ◽

J.A. Vasko-Moser ◽

I.E. James ◽

S.M. Blake ◽

...

Keyword(s):

Bone Resorption ◽

Bone Turnover ◽

Potent Inhibitor ◽

Cathepsin K

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Preferential and persistent impact of acute HIV-1 infection on CD4+ iNKT cells in colonic mucosa

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2104721118 ◽

2021 ◽

Vol 118 (46) ◽

pp. e2104721118

Author(s):

Dominic Paquin-Proulx ◽

Kerri G. Lal ◽

Yuwadee Phuang-Ngern ◽

Matthew Creegan ◽

Andrey Tokarev ◽

...

Keyword(s):

T Cells ◽

Peripheral Blood ◽

Colonic Mucosa ◽

Inkt Cells ◽

Elevated Expression ◽

Acute Hiv ◽

The Impact ◽

Hiv 1

Acute HIV-1 infection (AHI) results in the widespread depletion of CD4+ T cells in peripheral blood and gut mucosal tissue. However, the impact on the predominantly CD4+ immunoregulatory invariant natural killer T (iNKT) cells during AHI remains unknown. Here, iNKT cells from peripheral blood and colonic mucosa were investigated during treated and untreated AHI. iNKT cells in blood were activated and rapidly depleted in untreated AHI. At the time of peak HIV-1 viral load, these cells showed the elevated expression of cell death–associated transcripts compared to preinfection. Residual peripheral iNKT cells suffered a diminished responsiveness to in vitro stimulation early into chronic infection. Additionally, HIV-1 DNA, as well as spliced and unspliced viral RNA, were detected in iNKT cells isolated from blood, indicating the active infection of these cells in vivo. The loss of iNKT cells occurred from Fiebig stage III in the colonic mucosa, and these cells were not restored to normal levels after initiation of ART during AHI. CD4+ iNKT cells were depleted faster and more profoundly than conventional CD4+ T cells, and the preferential infection of CD4+ iNKT cells over conventional CD4+ T cells was confirmed by in vitro infection experiments. In vitro data also provided evidence of latent infection in iNKT cells. Strikingly, preinfection levels of peripheral blood CD4+ iNKT cells correlated directly with the peak HIV-1 load. These findings support a model in which iNKT cells are early targets for HIV-1 infection, driving their rapid loss from circulation and colonic mucosa.

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4-Methoxydalbergione is a potent inhibitor of human astroglioma U87 cells in vitro and in vivo

Acta Pharmacologica Sinica ◽

10.1038/s41401-020-00560-w ◽

2020 ◽

Author(s):

Ran Li ◽

Chang-qiong Xu ◽

Jian-xin Shen ◽

Qiu-yun Ren ◽

Di-ling Chen ◽

...

Keyword(s):

Potent Inhibitor ◽

U87 Cells

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Regulation of peripheral lipogenesis by glucagon. Inability of the hormone to inhibit lipogenesis in rat mammary acini in vitro in the presence or absence of agents which alter its effects on adipocytes

Biochemical Journal ◽

10.1042/bj2170743 ◽

1984 ◽

Vol 217 (3) ◽

pp. 743-749 ◽

Cited By ~ 19

Author(s):

N A Robson ◽

R A Clegg ◽

V A Zammit

Keyword(s):

Concentration Ratio ◽

Response Curve ◽

Potent Inhibitor ◽

Specific Binding ◽

Insulin Dose ◽

Mammary Glands ◽

Key Steps ◽

Glucagon Concentration

The rate of lipogenesis in acini isolated from mammary glands of mid-lactating rats was studied by measuring the rate of incorporation of 3H from 3H2O into total lipid and fatty acids, with glucose as substrate. Glucagon did not affect the rate of lipogenesis in acini. Glucagon did not antagonize the maximal stimulatory effect of insulin, nor did it alter the insulin dose-response curve. Theophylline, at concentrations up to 20 mM, was a potent inhibitor of lipogenesis in acini. Glucagon did not augment the degree of inhibition of lipogenesis induced by 5 mM-theophylline. The results suggest that mammary-gland acini do not respond to glucagon in vitro under conditions in which the hormone induces inhibition of lipogenesis (the present paper) and of individual key steps in the lipogenic pathway in adipocytes [Zammit & Corstorphine (1982) Biochem. J. 208, 783-788; Green (1983) Biochem. J. 212, 189-195]. In agreement with these observations, we could detect only a minimal degree of specific binding of 125I-labelled glucagon to acini which bound insulin normally. This difference in responsiveness of mammary and adipose cell preparations in vitro to glucagon suggests that the two tissues may be differentially responsive to changes in the circulating insulin/glucagon concentration ratio in vivo. The significance of these findings for the regulation of substrate utilization for lipogenesis in the two tissues during lactation is discussed.

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In vitro and in vivo Metabolism of a Potent Inhibitor of Soluble Epoxide Hydrolase, 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea

Frontiers in Pharmacology ◽

10.3389/fphar.2019.00464 ◽

2019 ◽

Vol 10 ◽

Cited By ~ 5

Author(s):

Debin Wan ◽

Jun Yang ◽

Cindy B. McReynolds ◽

Bogdan Barnych ◽

Karen M. Wagner ◽

...

Keyword(s):

Epoxide Hydrolase ◽

Potent Inhibitor ◽

Soluble Epoxide Hydrolase ◽

In Vivo Metabolism

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Pharmacology of MK-0591 (3-[1-(4-chlorobenzyl)-3-(t-butylthio)-5-(quinolin-2-yl-methoxy)-indol-2-yl]-2,2-dimethyl propanoic acid), a potent, orally active leukotriene biosynthesis inhibitor

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y92-107 ◽

1992 ◽

Vol 70 (6) ◽

pp. 799-807 ◽

Cited By ~ 79

Author(s):

C. Brideau ◽

C. Chan ◽

S. Charleson ◽

D. Denis ◽

J. F. Evans ◽

...

Keyword(s):

Polymorphonuclear Leukocytes ◽

Potent Inhibitor ◽

Ex Vivo ◽

Late Phase ◽

Squirrel Monkeys ◽

Propanoic Acid ◽

Orally Active

MK-0591 (3-[1-(4-chlorobenzyl)-3-(t-butylthio)-5-(quinolin-2-yl-methoxy)-indol-2-yl]-2,2-dimethyl propanoic acid, previously L-686,708) is a potent inhibitor of leukotriene (LT) biosynthesis in intact human and elicited rat polymorphonuclear leukocytes (PMNLs) (IC50 values 3.1 and 6.1 nM, respectively) and in human, squirrel monkey, and rat whole blood (IC50 values 510, 69, and 9 nM, respectively). MK-0591 had no effect on rat 5-lipoxygenase. MK-0591 has a high affinity for 5-lipoxygenase activating protein (FLAP) as evidenced by an IC50 value of 1.6 nM in a FLAP binding assay and inhibition of the photoaffinity labelling of FLAP by two different photoaffinity ligands. Inhibition of activation of 5-lipoxygenase was shown through inhibition of the translocation of the enzyme from the cytosol to the membrane in human PMNLs. MK-0591 was a potent inhibitor of LT biosynthesis in vivo, first, following ex vivo challenge of blood obtained from treated rats and squirrel monkeys, second, in a rat pleurisy model, and, third, as monitored by inhibition of the urinary excretion of LTE4 in antigen-challenged allergic sheep. Inhibition of antigen-induced bronchoconstriction by MK-0591 was observed in inbred rats pretreated with methysergide, Ascaris-challenged squirrel monkeys, and Ascaris-challenged sheep (early and late phase response). These results indicate that MK-0591 is a potent inhibitor of LT biosynthesis both in vitro and in vivo indicating that the compound will be suitable for assessing the role of leukotrienes in pathological situations.Key words: leukotriene, 5-lipoxygenase, leukotriene inhibitor, bronchoconstriction, inflammation, 5-lipoxygenase activating protein.

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