Inhibition of IgE-mediated histamine release by myosin light chain kinase inhibitors

Kitani, Seiichi; Teshima, Reiko; Morita, Yutaka; Itō, Kōji; Matsuda, Yuzuru; Nonomura, Yoshiaki

doi:10.1016/0006-291x(92)91607-r

Cited by 41 publications

(19 citation statements)

References 18 publications

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“…Maximal responses of exocytosis wi h antigen or A23187 were 63% of the total and 42%, respectively. These results are similar to the results of release of histamine, 5-hydroxytryptamine, or [3-hexosaminidase in previous reports [13,18,19,28,30].…”

Section: Visualization Of Exocytotic Process In Rbl-2h3 Cellssupporting

confidence: 92%

Quantitative analysis of exocytosis visualized by a video‐enhanced light/fluorescence microscope reveals two distinct components of exocytosis in RBL‐2H3 cells

et al. 1996

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Rat basophilic leukemia (RBL-2H3) cells, which exhibit Ca2+-dependent secretion of granules when stimulated with antigen or the Ca2+-ionophore A23187, were observed under a video-enhanced light/fluorescence microscope. Exocytotic events of individual granules were visualized in individual cells stimulated with antigen or A23187. Exocytosis of granules stimulated with A23187 showed two peaks in the time course. The earlier one was inhibited by selective inhibitors of protein kinase C (Ro31-8425, Ro31-8220, and chelerythrine) and the other was inhibited by an inhibitor of phosphatidate hydrolase, propranolol. Exocytosis by antigen stimulation, however, showed only one peak, which was inhibited by the selective inhibitors of protein kinase C, but not by propranolol. These results indicate that at least two distinct components of exocytosis exist in RBL-2H3 cells.

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Section: Visualization Of Exocytotic Process In Rbl-2h3 Cellssupporting

confidence: 92%

Quantitative analysis of exocytosis visualized by a video‐enhanced light/fluorescence microscope reveals two distinct components of exocytosis in RBL‐2H3 cells

et al. 1996

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“…In initial experiments, we confirmed the effects of wortmannin on FcERl-mediated responses, as previously reported by Kitani et al (1992) and Yano et al (1993). Using PtdIns as a substrate, we found that PI 3-kinase activity measured in anti-p85 immune comVol.…”

Section: Resultssupporting

confidence: 77%

“…In agreement with Kitani et al (1992), the inhibition of receptor-mediated secretion does not appear to be directly related to reduction in [Ca2+Ij, because the overall elevation of [Ca2+] is only mildly affected by wortmannin. Wortmannin is the first reagent to dissociate the dorsal ruffling response to FcER1 cross-linking from the spreading and actin plaque assembly responses that occur at the ventral surface.…”

Section: Discussionsupporting

confidence: 61%

“…Similarly, pretreatment of cells with 10 nM wortmannin resulted in -80% inhibition of 3H secretion in response to antigen. Like Kitani et al (1992) Wortmannin Reduces Antigen-induced IP3 Synthesis The synthesis of Ins(1,4,5)P3 is required for Ca2+ stores release and thus is a critical event in the FcERl-signaling pathway. We used a competitive radioligand receptor binding assay to specifically measure the 1,4,5 isomer of InsP3 present in cell lysates prepared from untreated and wortmannin-treated cells following FcERl activation.…”

Section: Resultsmentioning

confidence: 99%

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Wortmannin blocks lipid and protein kinase activities associated with PI 3-kinase and inhibits a subset of responses induced by Fc epsilon R1 cross-linking.

Barker

Caldwell

Hall

et al. 1995

MBoC

127

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We have investigated the effects of wortmannin, an inhibitor of phosphatidylinositol 3-kinase (PI 3-kinase), on antigen-mediated signaling in the RBL-2H3 mast cell model. In RBL-2H3 cells, the cross-linking of high affinity IgE receptors (FcER1) activates at least two cytoplasmic protein tyrosine kinases, Lyn and Syk, and stimulates secretion, membrane ruffling, spreading, pinocytosis, and the formation of actin plaques implicated in increased cell-substrate adhesion. In addition, FcER1 cross-linking activates PI 3-kinase. It was previously shown that wortmannin causes a dose-dependent inhibition of PI 3-kinase activity and also inhibits antigen-stimulated degranulation. We report that the antigen-induced synthesis of inositol(1,4,5)P3 is also markedly inhibited by wortmannin. Consistent with evidence in other cell systems implicating phosphatidylinositol(3,4,5)P3 in ruffling, pretreatment of

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“…Recent studies by Nonomura and colleagues showed that wortmannin, an inhibitor of myosin light chain kinase (MLCK), exerts inhibitory e ects on various exocytic events: histamine secretion from rat basophilic leukaemia (RBL-2H3) cells (Kitani et al, 1992;Ozawa et al, 1996), catecholamine secretion from bovine adrenal chroma n cells (Ohara-Imaizumi et al, 1992;Kumakura et al, 1994), insulin secretion from pancreatic b cell line MIN6 (Hagiwara et al, 1995), and the release of human immunode®ciency virus type 1 from host cells (Sasaki et al, 1995). These results suggest that phosphorylation of myosin II is involved in these exocytic events.…”

Section: Introductionmentioning

confidence: 99%

Differential effects of wortmannin on the release of substance P and amino acids from the isolated spinal cord of the neonatal rat

Suzuki

Yoshioka

Maehara

et al. 1998

British J Pharmacology

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1 E ects of wortmannin, an inhibitor of myosin light chain kinase, on the release of substance P and amino acids, GABA and glutamate, were investigated in the isolated spinal cord preparation of the neonatal rat. 2 Wortmannin at 0.5 ± 10 mM depressed the release of substance P evoked by high-K + (90 mM) medium from the spinal cord (IC 50 =1.1 mM). Wortmannin also depressed the high-K + (70 mM)-evoked release of substance P from cultured dorsal root ganglion neurons of neonatal rats. In contrast, the high-K + (90 mM)-evoked release of GABA and glutamate from the spinal cord was not a ected by wortmannin (0.1 ± 10 mM). 3 Upon stimulation of a dorsal root, a monosynaptic re¯ex and a subsequent slow ventral root depolarization were evoked in the ipsilateral ventral root of the same segment in the isolated spinal cord preparation. The magnitude of the slow ventral root depolarization was depressed gradually to about 70% of the control during the course of 30 min under wortmannin (1 mM). In contrast, the monosynaptic re¯ex was una ected by wortmannin. 4 Immuno¯uorescent staining revealed that immunoreactivities of substance P and myosin II were colocalized at presynaptic terminals in the dorsal horn of the neonatal rat spinal cord. 5 The present results suggest that myosin phosphorylation by myosin light chain kinase may play a crucial role in the release of substance P, but not in the release of GABA and glutamate in the neonatal rat spinal cord. This may re¯ect a di erence in the exocytic mechanisms of substance Pcontaining large dense core vesicles and amino acid-containing small clear vesicles.

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Inhibition of IgE-mediated histamine release by myosin light chain kinase inhibitors

Cited by 41 publications

References 18 publications

Quantitative analysis of exocytosis visualized by a video‐enhanced light/fluorescence microscope reveals two distinct components of exocytosis in RBL‐2H3 cells

Quantitative analysis of exocytosis visualized by a video‐enhanced light/fluorescence microscope reveals two distinct components of exocytosis in RBL‐2H3 cells

Wortmannin blocks lipid and protein kinase activities associated with PI 3-kinase and inhibits a subset of responses induced by Fc epsilon R1 cross-linking.

Differential effects of wortmannin on the release of substance P and amino acids from the isolated spinal cord of the neonatal rat

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