title: Ins(3,4,5,6)P4 specifically inhibits a receptor-mediated Ca2+-dependent Cl- current in CFPAC-1 cells.
abstract: We have examined the role of inositol 3,4,5,6-tetrakisphosphate [Ins(3,4,5,6)P4] in the control of Cl- current in CFPAC-1 cells. Intracellular Ins(3,4,5,6)P4 had no effect on basal current, but it produced a five- to sevenfold reduction in the Cl- current stimulated by either 2 microM extracellular ATP or by 1 microM extracellular thapsigargin. The half-maximally effective dose of Ins(3,4,5,6)P4 was 2.9 microM, and 4 microM blocked >80% of the ATP-activated current. In contrast, 10 microM Ins(1,4,5,6)P4, Ins(1,3,4,5)P4, or Ins(1,3,4,6)P4 enhanced rather than inhibited the ATP-activated Cl- current, although Ins(1,4,5,6)P4 only acted transiently. These stimulatory effects were Ca2+ dependent and largely inhibited by coapplication of equimolar Ins(3,4,5,6)P4. Inositol 1,3,4,5,6-pentakisphosphate, the precursor of Ins(3,4,5,6)P4, did not affect Cl- current. These data consolidate and extend the hypothesis that Ins(3,4,5,6)P4 is an important intracellular regulator of Cl- current in epithelial cells.
authors.affiliation: Department of Physiology, University of Alberta, Edmonton, Canada.
authors.forename: M W
authors.initials: MW
authors.lastname: Ho
authors.forename: S B
authors.initials: SB
authors.lastname: Shears
authors.forename: K S
authors.initials: KS
authors.lastname: Bruzik
authors.forename: M
authors.initials: M
authors.lastname: Duszyk
authors.forename: A S
authors.initials: AS
authors.lastname: French
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D018270:Carcinoma, Ductal, Breast / Q000150:complications / Q000473:pathology; D018118:Chloride Channels / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000502:physiology*; D003550:Cystic Fibrosis / Q000150:complications / Q000473:pathology; D004594:Electrophysiology; D006801:Humans; D007295:Inositol Phosphates / Q000494:pharmacology*; D010190:Pancreatic Neoplasms / Q000150:complications / Q000473:pathology; D011956:Receptors, Cell Surface / Q000502:physiology*; D014407:Tumor Cells, Cultured
chemical_list: D018118:Chloride Channels; D007295:Inositol Phosphates; D011956:Receptors, Cell Surface; C081652:inositol-3,4,5,6-tetrakisphosphate; D000255:Adenosine Triphosphate; D002118:Calcium