Inhibition of histamine secretion by wortmannin through the blockade of phosphatidylinositol 3-kinase in RBL-2H3 cells.

Yano, Hiroshi; Nakanishi, Satoshi; Kimura, Koutarou D.; Hanai, Nobuo; Saitoh, Yutaka; Fukui, Yoshihiro; Nonomura, Yoshiaki; Matsuda, Yuzuru

doi:10.1016/s0021-9258(19)74466-4

Cited by 687 publications

(95 citation statements)

References 71 publications

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“…These two compounds are currently undergoing phase I/II clinical trials for solid tumors [44][45][46]. Table 3 shows that IC 50 values determined by CE were comparable to the values determined by kit assays and reported in the literature [20,[23][24][25][26][27][28][29][30]. The tested compounds have a wide range of IC 50 values toward PI3K isoforms, going from a few nanomolars to a few micromolars.…”

Section: Evaluation Of the Ce-based Kinase Assay Methods On Pi3kαsupporting

confidence: 63%

“…The IC 50 , Z′,an dr 2 values obtained are also summarized in Table 1. All the assays yielded IC 50 values comparable to those reported in the literature [16,20,23,24,29]. However, the results obtained with the HTRF PI3K TM kit cannot be considered trustworthy since Z′ was in some cases below 0.4.…”

Section: Evaluation Of the Ce-based Kinase Assay Methods On Pi3kαsupporting

confidence: 55%

“…For this purpose, a novel CE-based assay was first developed on the isoform α of PI3K and compared to five commercialized assay kits based on timeresolved fluorescence resonance energy transfer (TR-FRET) or bioluminescence. These kits are frequently used in the literature for kinase analysis [18][19][20][21][22][23][24][25][26][27][28][29][30] and are available in our laboratory. Assay performance was evaluated by testing three referenced PI3Kα inhibitors and by estimating their sensitivity (signal-to-background ration (S/B)), reproducibility (Z′), and robustness (r 2 ).…”

Section: Introductionmentioning

confidence: 99%

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New in-capillary electrophoretic kinase assays to evaluate inhibitors of the PI3k/Akt/mTOR signaling pathway

Nehmé

Saurat

et al. 2014

Anal Bioanal Chem

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Human kinases are one of the most promising targets for cancer therapy. Methods able to measure the effects of drugs on these cell agents remain crucial for biologists and medicinal chemists. The current work therefore sought to develop an in-capillary enzymatic assay based on capillary electrophoresis (CE) to evaluate the inhibition of phosphatidylinositol-3-kinase (PI3K), protein kinase B (Akt), and the mammalian target of rapamycin (mTOR). These kinases belong to the same signaling pathway PI3K/Akt/mTOR. For this proposal, the capillary was used as a nanoreactor in which a few nanoliters of the kinase, its substrate, adenosine triphosphate (ATP), and the potent inhibitor were separately injected. A transverse diffusion of laminar flow profiles (TDLFP) approach was employed to mix the reactants. Adenosine diphosphate (ADP ) was detected online at 254 nm. The CE assay was first developed on the α isoform of PI3K. It was compared to five commercial kits frequently used to assess kinase inhibition, based on time-resolved fluorescence resonance energy transfer (TR-FRET) and bioluminescence. Each assay was evaluated in terms of sensitivity (S/B), reproducibility (Z'), and variability (r (2)). This CE method was easily extended to assay the inhibition of the β, γ, and δ isoforms of PI3K, and of the other kinases of the pathway, Akt1 and mTOR, since it is based on in-capillary mixing by TDLFP and on ADP quantification by simple UV absorption. This work shows for the first time the evaluation of inhibitors of the kinases of the PI3K/Akt/mTOR pathway using a common in-capillary CE assay. Several inhibitors with a wide range of affinity toward these enzymes were tested.

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Section: Evaluation Of the Ce-based Kinase Assay Methods On Pi3kαsupporting

confidence: 63%

Section: Evaluation Of the Ce-based Kinase Assay Methods On Pi3kαsupporting

confidence: 55%

Section: Introductionmentioning

confidence: 99%

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New in-capillary electrophoretic kinase assays to evaluate inhibitors of the PI3k/Akt/mTOR signaling pathway

Nehmé

Saurat

et al. 2014

Anal Bioanal Chem

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“…In the present study, EGCG was used as a positive example of a natural typical inhibitor since its antiallergic effects are well reported (Tachibana, 2011) and that it is a food-grade phenolic compound comparable to dieckol. Several pharmaceutical reagents show strong antiallergic effects such as dexamethasone and wortmannin which exhibit strong suppression of mouse ear swelling and degranulation or chemical mediator release in RBL cells, respectively (Carlson et al, 1985;Ivetić Tkalčević et al, 2012;Nigorikawa et al, 2014;Yano et al, 1993). Compared to the dose used in present study, the efficacies of these pharmaceutical reagents would be comparable to and/or higher than that of dieckol.…”

Section: Discussionmentioning

confidence: 80%

Dieckol isolated from a brown alga,Eisenia nipponica, suppresses ear swelling from allergic inflammation in mouse

et al. 2021

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In developed countries, the incidence of allergies such as food allergy, asthma, atopic dermatitis, and hay fever has increase, becoming an acute problem (Platts-Mills, 2015). According to the Japanese Ministry of Health, Labor, and Welfare, half of the Japanese people may suffer from allergies, making them a societal problem (Taniguchi, 2012). Natural remedies and foods possessing antiallergic and anti-inflammatory effects are highly sought-after and recently researchers have endeavored to identify natural compounds and products with antiallergic properties.Prebiotics and probiotics, such as dietary fibers (e.g., oligosaccharides) and lactic acid bacteria, are known to exert antiallergic effects through gut-based immunomodulation (Hardy et al., 2013).Phenolic compounds (polyphenols) are another well-known group of natural antiallergic compounds derived from food products. For

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“…Wortmannin is a nonselective kinase inhibitor that inhibits myosin light chain kinase (Nakanishi et al, 1992) and phosphatidylinositol 3-kinase (PtdIns 3-kinase) (Yano et al, 1993). The latter is involved in the synthesis of phosphatidylinositol 3,4,5trisphosphate (PIP 3 ) from PIP 2 (Akasu et al, 1993).…”

Section: Inhibition Of Pip 2 Resynthesis Slows Recovery From G M Suppressionmentioning

confidence: 99%

Experiments to Test the Role of Phosphatidylinositol 4,5-Bisphosphate in Neurotransmitter-Induced M-Channel Closure in Bullfrog Sympathetic Neurons

et al. 2003

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Various neurotransmitters excite neurons by suppressing a ubiquitous, voltage-dependent, noninactivating K+ conductance called the M-conductance (gM). In bullfrog sympathetic ganglion neurons the suppression of gM by the P2Y agonist ATP involves phospholipase C (PLC). The present results are consistent with the involvement of the lipid and inositol phosphate cycles in the effects of both P2Y and muscarinic cholinergic agonists on gM. Impairment of resynthesis of phosphatidylinositol 4,5-bisphosphate (PIP2) with the phosphatidylinositol 4-kinase inhibitor wortmannin (10 microm) slowed or blocked the recovery of agonist-induced gM suppression. This effect could not be attributed to an action of wortmannin on myosin light chain kinase or on phosphatidylinositol 3-kinase. Inhibition of PIP2 synthesis at an earlier point in the lipid cycle by the use of R59022 (40 microm) to inhibit diacylglycerol kinase also slowed the rate of recovery of successive ATP responses. This effect required several applications of agonist to deplete levels of various phospholipid intermediates in the lipid cycle. PIP2 antibodies attenuated the suppression of gM by agonists. Intracellular application of 20 microm PIP2 slowed the rundown of KCNQ2/3 currents expressed in COS-1 or tsA-201 cells, and 100 microm PIP2 produced a small potentiation of native M-current bullfrog sympathetic neurons. These are the results that might be expected if agonist-induced activation of PLC and the concomitant depletion of PIP2 contribute to the excitatory action of neurotransmitters that suppress gM.

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Inhibition of histamine secretion by wortmannin through the blockade of phosphatidylinositol 3-kinase in RBL-2H3 cells.

Cited by 687 publications

References 71 publications

New in-capillary electrophoretic kinase assays to evaluate inhibitors of the PI3k/Akt/mTOR signaling pathway

New in-capillary electrophoretic kinase assays to evaluate inhibitors of the PI3k/Akt/mTOR signaling pathway

Dieckol isolated from a brown alga,Eisenia nipponica, suppresses ear swelling from allergic inflammation in mouse

Experiments to Test the Role of Phosphatidylinositol 4,5-Bisphosphate in Neurotransmitter-Induced M-Channel Closure in Bullfrog Sympathetic Neurons

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