Effect of okadaic acid on immunologic and non-immunologic histamine release in rat mast cells

Estévez, M. D.; Vieytes, Mercedes R.; Louzao, M. Carmen; Botana, Luís M.

doi:10.1016/0006-2952(94)90194-5

Cited by 26 publications

(15 citation statements)

References 15 publications

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“…When rat mast cells were challenged with antigen. OA inhibited IgE-mediated histamine release from rat mast cells as described previously [26,27]. Thus the effect of OA is dependent on the type of cell and the degree of crosslinkage.…”

Section: Oa Effects On Basophils/mast Cellssupporting

confidence: 72%

“…While this study was in progress, OA was report ed to inhibit histamine release from human basophils, lung mast cells and rat mast cells. However, the reports did not show definite results and comparative studies [12,13,[26][27][28], Using a mucosal mast cell line (RBL-2H3), our studies provided several new insights into the role o f serine/threonine phosphatase in basophils/mast cells.…”

Section: Discussionmentioning

confidence: 69%

“…OA inhibited IgE-mediated histamine release when cells were sensitized with DNP-lgE and challenged with multivalent DNP4SBSA as observed perviously (ICj": 6.6±4.6 pA/, percent inhib ition: 55.1 ±4.7 at 12.5 pAf ofOA, n = 3) [27]. Then we used the monoclonal antibody against FceRI (BA3) which cross-linked two receptors for the challenge to see the difference o f action of OA.…”

Section: The Effect Ojoa On Histamine Release From Rat Peritoneal Masmentioning

confidence: 76%

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The Effect of Okadaic Acid on Histamine Release, Cell Morphology and Phosphorylation in Rat Basophilic Leukemia (RBL-2H3) Cells, Human Basophils and Rat Peritoneal Mast Cells

Kitani

Teshima²,

Nonomura³

et al. 1996

Int Arch Allergy Immunol

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To study the involvement of serine/threonine phosphatase in the signal transduction of mast cells, we examined the effects of okadaic acid (OA), an inhibitor of type-1 and -2A phosphatase on histamine release, cell morphology, calcium influx and protein phosphorylation of rat basophilic leukemia (RBL-2H3) cells, human basophils and rat peritoneal mast cells. OA inhibited IgE-mediated histamine release from RBL-2H3 cells and human basophils dose-dependently. There was a remarkable enhancement of IgE-mediated histamine release when rat peritoneal mast cells were suboptimally challenged. OA induced a marked change of cell features, detached RBL-2H3 cells from plastic well and kept the 18- and 68-kD proteins phosphorlyated. These findings show that phosphatase may play a role in the modulation of secretion in mast cells.

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Section: Oa Effects On Basophils/mast Cellssupporting

confidence: 72%

Section: Discussionmentioning

confidence: 69%

Section: The Effect Ojoa On Histamine Release From Rat Peritoneal Masmentioning

confidence: 76%

See 1 more Smart Citation

The Effect of Okadaic Acid on Histamine Release, Cell Morphology and Phosphorylation in Rat Basophilic Leukemia (RBL-2H3) Cells, Human Basophils and Rat Peritoneal Mast Cells

Kitani

Teshima²,

Nonomura³

et al. 1996

Int Arch Allergy Immunol

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“…Despite these misgivings, okadaic acid continues to be a useful investigative tool not least because it is cell permeant (Haystead et al, 1989;Hardie et al, 1991 Pharmacology (1996) , 1990). More recently okadaic acid has been shown to inhibit IgE-dependent mediator release from rat peritoneal mast cells (Estevez et al, 1994), human lung mast cells (Peachell & Munday, 1993), human basophils (Botana & MacGlashan, 1993) and to activate RBL-2H3 cells (Sakamoto et al, 1994 Hypotonic lysis buffer contained: Tris 50 mM, EDTA 1 mM, EGTA 0.1 mM, DTT 0.5 mM, PMSF 50 pg ml-', soybean trypsin inhibitor 50 pg ml-', leupeptin 5 pg ml-' and aprotinin 5 pg ml-'. The pH was titrated to 8.0.…”

Section: Introductionmentioning

confidence: 99%

Regulation of human basophil function by phosphatase inhibitors

Peirce

Warner

Munday³

et al. 1996

British J Pharmacology

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Okadaic acid, a cell permeant inhibitor of protein serine/threonine phosphatases (PPs), attenuated the IgE‐mediated release of the pre‐formed mediator, histamine from human basophils in a time‐ and dose‐dependent manner. Optimal inhibition (77 ± 4%, P < 0.0001) of histamine release was observed following a 2 h incubation with 1 μm okadaic acid. Okadaic acid and two analogues of okadaic acid were also studied and were found to inhibit the IgE‐dependent release of histamine. Concentrations required to inhibit release by 50% (IC50) were 0.6 μm for okadaic acid and 7.5 μm for okadaol, whereas okadaone was inactive. The structurally‐unrelated PP inhibitor, calyculin A, also inhibited IgE‐dependent histamine release from basophils dose‐dependently and was approximately six fold more potent than okadaic acid. The IgE‐mediated generation of sulphopeptidoleukotrienes (sLT) from basophils was inhibited by okadaic acid and related analogues with the following rank order of potency; okadaic acid (approx. IC50 0.3 μm) > okadaol (3 μm) > okadaone (inactive). Okadaic acid, okadaol and okadaone (all at 3 μm) inhibited the IgE‐mediated generation of the cytokine interleukin 4 (IL4) from human basophils by 67 ± 9% (P < 0.002), 48 ± 14% (P < 0.05) and 8 ± 7% (P = 0.31), respectively. Extracts of purified human basophils liberated 32P from radiolabeled glycogen phosphorylase and this PP activity was inhibited by 17 ± 3% (P < 0.0005) by a low (2 nM) concentration of okadaic acid and was inhibited by 96 ± 1% (P < 0.0001) by a higher (5 μm) concentration of okadaic acid. Because a low (2 nM) concentration of okadaic acid inhibits PP2A selectively whereas a higher (5 μm) concentration inhibits both PP1 and PP2A, these findings suggest that both PP1 and PP2A are present in basophils. In total these data suggest that PPs are resident in human basophils and that PPs may be important in the regulation of basophil function.

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“…Much of the current information about intracellular signaling in mast cells has come from the rat basophilic leukemia cell line, RBL-2H3, which is homologous to mucosal mast cells (6). Recent work in RBL-2H3 cells as well as rat peritoneal mast cells and human lung mast cells has implicated serine/threonine protein phosphatases in the regulation of the secretory process (7)(8)(9)(10)(11).…”

mentioning

confidence: 99%

Transient Translocation and Activation of Protein Phosphatase 2A during Mast Cell Secretion

Ludowyke¹,

Holst²,

Mudge³

et al. 2000

Journal of Biological Chemistry

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Okadaic acid inhibits secretion from mast cells, suggesting a regulatory role for protein Ser/Thr phosphatases type I (PP1) and/or 2A (PP2A) in the secretory process. In unstimulated RBL-2H3 cells, okadaic acid pretreatment inhibited PP2A activity in both cytosol and membrane fractions, but inhibition of secretion correlated with inhibition of membrane-bound rather than cytosolic PP2A activity. Okadaic acid had very little effect on PP1 activity. Stimulation of RBL-2H3 cells by antigen led to the activity and amount of PP2A in the membrane fraction increasing nearly 2-fold. In contrast, there was little change in the activity or distribution of PP1. Importantly, the translocation of PP2A was transient, coinciding with or marginally preceding the peak rate of secretion, suggesting a link between PP2A translocation, activity, and secretion. Phorbol 12-myristate 13-acetate plus the calcium ionophore A23187 induced a slower, prolonged rate of secretion that coincided with a similarly protracted translocation of PP2A to the membrane fraction. PP2A translocation is not the only event required for secretion as translocation was also induced by phorbol 12-myristate 13-acetate, without resulting in secretion. These results indicate that increased protein dephosphorylation in the membrane fraction mediated by PP2A is required for mast cell secretion. To our knowledge, this is the first demonstration of a signalmediated, rapid, transient translocation and activation of PP2A in membranes in any system.

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Effect of okadaic acid on immunologic and non-immunologic histamine release in rat mast cells

Cited by 26 publications

References 15 publications

The Effect of Okadaic Acid on Histamine Release, Cell Morphology and Phosphorylation in Rat Basophilic Leukemia (RBL-2H3) Cells, Human Basophils and Rat Peritoneal Mast Cells

The Effect of Okadaic Acid on Histamine Release, Cell Morphology and Phosphorylation in Rat Basophilic Leukemia (RBL-2H3) Cells, Human Basophils and Rat Peritoneal Mast Cells

Regulation of human basophil function by phosphatase inhibitors

Transient Translocation and Activation of Protein Phosphatase 2A during Mast Cell Secretion

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