ArticleProceedings of the National Academy of Sciences of the United States of America1996
A biologic function for an "orphan" messenger: D-myo-inositol 3,4,5,6-tetrakisphosphate selectively blocks epithelial calcium-activated chloride channels.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1996. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 98 citations in OpenAlex.
- Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine.Nature genetics · 2016Pooled it
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- Convergent Evolution of the Osmoregulation System in Decapod Shrimps.Marine biotechnology (New York, N.Y.) · 2017Article
- Inositol Polyphosphate Kinases, Fungal Virulence and Drug Discovery.Journal of fungi (Basel, Switzerland) · 2016Review
- Defining signal transduction by inositol phosphates.Sub-cellular biochemistry · 2012Review
- Expression of DeltaF508 Cystic Fibrosis Transmembrane Regulator (CFTR) Decreases Membrane Sialylation.The open respiratory medicine journal · 2009Article
- Molecular basis for the integration of inositol phosphate signaling pathways via human ITPK1.Advances in enzyme regulation · 2009Review
- Inositol polyphosphate derivative inhibits Na+ transport and improves fluid dynamics in cystic fibrosis airway epithelia.American journal of physiology. Cell physiology · 2005Article
- The CLCA gene locus as a modulator of the gastrointestinal basic defect in cystic fibrosis.Human genetics · 2004Article
- How versatile are inositol phosphate kinases?The Biochemical journal · 2004Review
- The Ca-activated Cl channel and its control in rat olfactory receptor neurons.The Journal of general physiology · 2003Article
- State and spectral properties of chloride oscillations in pollen.Biophysical journal · 2003Article
- Multitasking in signal transduction by a promiscuous human Ins(3,4,5,6)P(4) 1-kinase/Ins(1,3,4)P(3) 5/6-kinase.The Biochemical journal · 2000Article
- New insights into the pathogenesis of intestinal dysfunction: secretory diarrhea and cystic fibrosis.World journal of gastroenterology · 2000Article
- Effect of Saccharomyces boulardii on cAMP- and Ca2+ -dependent Cl- secretion in T84 cells.Digestive diseases and sciences · 1999Article
- Regulation of Ca2+-dependent Cl- conductance in a human colonic epithelial cell line (T84): cross-talk between Ins(3,4,5,6)P4 and protein phosphatases.The Journal of physiology · 1998Article
- D-myo-Inositol 1,4,5,6-tetrakisphosphate produced in human intestinal epithelial cells in response to Salmonella invasion inhibits phosphoinositide 3-kinase signaling pathways.Proceedings of the National Academy of Sciences of the United States of America · 1997Article
- D-myo-inositol 1,4,5-trisphosphate 3-kinase A is activated by receptor activation through a calcium:calmodulin-dependent protein kinase II phosphorylation mechanism.The EMBO journal · 1997Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Inositol phosphates are a family of water-soluble intracellular signaling molecules derived from membrane inositol phospholipids. They undergo a variety of complex interconversion pathways, and their levels are dynamically regulated within the cytosol in response to a variety of agonists. Relatively little is known about the biological function of most members of this family, with the exception of inositol 1,4,5-trisphosphate. Specifically, the biological functions of inositol tetrakisphosphates are largely obscure. In this paper, we report that D-myo-inositol 3,4,5,6-tetrakisphosphate (D-Ins(3,4,5,6)P4) has a direct biphasic (activation/inhibition) effect on an epithelial Ca(2+)-activated chloride channel. The effect of D-Ins(3,4,5,6)P4 is not mimicked by other inositol tetrakisphosphate isomers, is dependent on the prevailing calcium concentration, and is influenced when channels are phosphorylated by calmodulin kinase II. The predominant effect of D-Ins(3,4,5,6)P4 on phosphorylated channels is inhibitory at levels of intracellular calcium observed in stimulated cells. Our findings indicate the biological function of a molecule hitherto considered as an "orphan" messenger. They suggest that the molecular target for D-Ins(3,4,5,6)P4 is a plasma membrane Ca(2+)-activated chloride channel. Regulation of this channel by D-Ins(3,4,5,6)P4 and Ca2+ may have therapeutic implications for the disease states of both diabetic nephropathy and cystic fibrosis.
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