Long-term uncoupling of chloride secretion from intracellular calcium levels by Ins(3,4,5,6)P4

Mana Vajanaphanich, Carsten Schultz, Marco T. Rudolf, Matthew Wasserman, P. Enyedi, Andrew Craxtonl, Stephen B. Shears, Roger Y. Tsien, Kim E. Barrett, Alexis Traynor-Kaplan

Research output: Contribution to journalArticle

162 Citations (Scopus)

Abstract

Osmoregulation, inhibitory neurotransmission and pH balance depend on chloride ion (Cl-) flux. In intestinal epithelial cells, apical Cl- channels control salt and fluid secretion and are, in turn, regulated by agonists acting through cyclic nucleotides and internal calcium ion concentration ([Ca2+](i)). Recently, we found that muscarinic pretreatment prevents [Ca2+](i) increases from eliciting Cl- secretion in T84 colonic epithelial cells. By studying concomitant inositol phosphate metabolism, we have now identified D-myo-inositol 3,4,5,6-tetrakisphosphate (Ins(3,4,5,6)P4), as the inositol phosphate most likely to mediate this uncoupling. A novel, membrane-permeant ester prepared by total synthesis delivers Ins(3,4,5,6)P4 intracellularly and confirms that this emerging messenger does inhibit Cl- flux resulting from thapsigargin- or histamine-induced ]Ca2+](i) elevations.

Original languageEnglish
Pages (from-to)711-714
Number of pages4
JournalNature
Volume371
Issue number6499
DOIs
Publication statusPublished - Oct 20 1994

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Inositol Phosphates
Chlorides
Epithelial Cells
Ions
Calcium
Osmoregulation
Fluids and Secretions
Thapsigargin
Cyclic Nucleotides
Synaptic Transmission
Cholinergic Agents
Histamine
Esters
Salts
Membranes
inositol-3,4,5,6-tetrakisphosphate
D-myo-inositol 3,4,5,6-tetrakisphosphate

ASJC Scopus subject areas

  • General

Cite this

Vajanaphanich, M., Schultz, C., Rudolf, M. T., Wasserman, M., Enyedi, P., Craxtonl, A., ... Traynor-Kaplan, A. (1994). Long-term uncoupling of chloride secretion from intracellular calcium levels by Ins(3,4,5,6)P4. Nature, 371(6499), 711-714. https://doi.org/10.1038/371711a0

Long-term uncoupling of chloride secretion from intracellular calcium levels by Ins(3,4,5,6)P4. / Vajanaphanich, Mana; Schultz, Carsten; Rudolf, Marco T.; Wasserman, Matthew; Enyedi, P.; Craxtonl, Andrew; Shears, Stephen B.; Tsien, Roger Y.; Barrett, Kim E.; Traynor-Kaplan, Alexis.

In: Nature, Vol. 371, No. 6499, 20.10.1994, p. 711-714.

Research output: Contribution to journalArticle

Vajanaphanich, M, Schultz, C, Rudolf, MT, Wasserman, M, Enyedi, P, Craxtonl, A, Shears, SB, Tsien, RY, Barrett, KE & Traynor-Kaplan, A 1994, 'Long-term uncoupling of chloride secretion from intracellular calcium levels by Ins(3,4,5,6)P4', Nature, vol. 371, no. 6499, pp. 711-714. https://doi.org/10.1038/371711a0
Vajanaphanich M, Schultz C, Rudolf MT, Wasserman M, Enyedi P, Craxtonl A et al. Long-term uncoupling of chloride secretion from intracellular calcium levels by Ins(3,4,5,6)P4. Nature. 1994 Oct 20;371(6499):711-714. https://doi.org/10.1038/371711a0
Vajanaphanich, Mana ; Schultz, Carsten ; Rudolf, Marco T. ; Wasserman, Matthew ; Enyedi, P. ; Craxtonl, Andrew ; Shears, Stephen B. ; Tsien, Roger Y. ; Barrett, Kim E. ; Traynor-Kaplan, Alexis. / Long-term uncoupling of chloride secretion from intracellular calcium levels by Ins(3,4,5,6)P4. In: Nature. 1994 ; Vol. 371, No. 6499. pp. 711-714.
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