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

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

Research output: Contribution to journalArticlepeer-review

178 Scopus citations


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)1-3. Recently, we found that muscarinic pretreatment prevents [Ca2 +]i increases from eliciting Cl- secretion in T84 colonic epithelial cells4. 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 messenger5 does inhibit Cl- flux resulting from thapsigargin- or histamine-induced [Ca2 +]i elevations.

Original languageEnglish (US)
Pages (from-to)711-714
Number of pages4
Issue number6499
StatePublished - 1994
Externally publishedYes

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