Antagonists of myo-inositol 3,4,5,6-tetrakisphosphate allow repeated epithelial chloride secretion

Rudolf, Marco T.; Dinkel, Carlo; Traynor‐Kaplan, Alexis; Schultz, Carsten

doi:10.1016/s0968-0896(03)00188-3

Cited by 22 publications

(17 citation statements)

References 38 publications

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“…Cell-permeant antagonists of Ins(3,4,5,6)P 4 are being developed for the purpose of enhancing CaCC activity and thereby improving salt-and fluid-secretion in CF airways (Rudolf et al, 2003). Upregulation of CaCCs may have the added benefit of secondarily inhibiting Na + uptake, which further assists this approach to CF therapy (Moody et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

“…We specifically elevated intracellular levels of Ins(3,4,5,6)P 4 by treating the monolayer culture with a cell-permeable, bio-activatable analogue of this inositol phosphate (Vajanaphanich et al, 1994;Rudolf et al, 2003). This type of experiment has previously only been performed in two cell lines, in T 84 colonic epithelia and CFPAC-1 pancreatic epithelia (Vajanaphanich et al, 1994;Carew et al, 2000).…”

Section: Insmentioning

confidence: 99%

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Apical localization of ITPK1 enhances its ability to be a modifier gene product in a murine tracheal cell model of cystic fibrosis

Yang

Reece

Gabriel

et al. 2006

Journal of Cell Science

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A new aspect of research into the pathogenesis of cystic fibrosis (CF) is a genetics-based search for `modifier genes' that may affect the severity of CF lung disease. Using an alternative, cell biological approach, we show that ITPK1 should be considered a modifier gene. ITPK1 synthesizes an intracellular signal, inositol (3,4,5,6)-tetrakisphosphate [Ins(3,4,5,6)P4]. A bio-activatable, cell-permeable analogue of Ins(3,4,5,6)P4 inhibited Ca2+-dependent secretion of Cl- from polarized monolayers of immortalized mouse tracheal epithelial cells (MTEs). Analysis by high-pressure liquid chromatography showed endogenous Ins(3,4,5,6)P4 levels in CF MTEs were approximately 60% below those in wild-type MTEs (P<0.03). This adaptation, which improves purinergic activation of Ca2+-dependent Cl- secretion in CF MTEs, was exceptionally specific; there was no effect upon the cellular levels of all the other inositol phosphate signals. Real-time PCR provided the explanation: the level of ITPK1 expression in wild-type MTEs was twice as high as that in CF MTEs (P<0.002). The biological impact of this differential gene expression is amplified by ITPK1 being concentrated at the apical membrane of MTEs, which we discovered following confocal immunofluorescence microscopy. Compartmentalization of Ins(3,4,5,6)P4 synthesis adjacent to its site of action will enhance its regulatory capacity.

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Section: Discussionmentioning

confidence: 99%

Section: Insmentioning

confidence: 99%

Apical localization of ITPK1 enhances its ability to be a modifier gene product in a murine tracheal cell model of cystic fibrosis

Yang

Reece

Gabriel

et al. 2006

Journal of Cell Science

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“…Current evidence indicates that Ins(3,4,5,6)P 4 synthesis is linked to Ins(1,3,4,5,6)P 5 by a reversible phosphatase/ kinase cascade (Shears, 1998;Brearley and Hanke, 2000;Irvine and Schell, 2001). The function of Ins(3,4,5,6)P 4 was first identified in epithelial cells, where it specifically inhibits a Cl -channel that is involved in maintenance of cell volume and secretion (Shears, 1998;Ho et al, 2001;Rudolf et al, 2003;Mitchell et al, 2008). Cl -channels have crucial roles in plant cell osmoregulation (Teodoro et al, 1998;Shabala et al, 2000;White and Broadley, 2001).…”

Section: +mentioning

confidence: 99%

Spatial and temporal integration of signalling networks regulating pollen tube growth

Zonia

2010

Journal of Experimental Botany

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The overall function of a cell is determined by its contingent of active signal transduction cascades interacting on multiple levels with metabolic pathways, cytoskeletal organization, and regulation of gene expression. Much work has been devoted to analysis of individual signalling cascades interacting with unique cellular targets. However, little is known about how cells integrate information across hierarchical signalling networks. Recent work on pollen tube growth indicates that several key signalling cascades respond to changes in cell hydrodynamics and apical volume. Combined with known effects on cytoarchitecture and signalling from other cell systems, hydrodynamics has the potential to integrate and synchronize the function of the broader signalling network in pollen tubes. This review will explore recent work on cell hydrodynamics in a variety of systems including pollen, and discuss hydrodynamic regulation of cell signalling and function including exocytosis and endocytosis, actin cytoskeleton reorganization, cell wall deposition and assembly, phospholipid and inositol polyphosphate signalling, ion flux, small G-proteins, fertilization, and self-incompatibility. The combined data support a newly emerging model of pollen tube growth.

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“…10). Most work so far has been done on ion chelators (Grynkiewicz et al, 1985;Tsien, 1981), nucleotides (Friis and Bundgaard, 1996;Peyrottes et al, 2004;Schultz, 2003;Schultz et al, 1994Schultz et al, , 1993, inositol phosphates (Li et al, 1998;Rudolf et al, 2003;Vajanaphanich et al, 1994), phosphoinositides (Dinkel et al, 2001;Jiang et al, 1998), and other lipid derivatives . In addition, some small molecule sensor molecules (Wichmann et al, 2006;Zlokarnik et al, 1998) but also some commercial drugs rely on this technique (Krapcho et al, 1988;Starret et al, 1994;von Daehne et al, 1970).…”

Section: Membrane Permeabilitymentioning

confidence: 99%

Molecular tools for cell and systems biology

Schultz

2007

HFSP Journal

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Antagonists of myo-inositol 3,4,5,6-tetrakisphosphate allow repeated epithelial chloride secretion

Cited by 22 publications

References 38 publications

Apical localization of ITPK1 enhances its ability to be a modifier gene product in a murine tracheal cell model of cystic fibrosis

Apical localization of ITPK1 enhances its ability to be a modifier gene product in a murine tracheal cell model of cystic fibrosis

Spatial and temporal integration of signalling networks regulating pollen tube growth

Molecular tools for cell and systems biology

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