Emptying of intracellular Ca2+ stores releases a novel small messenger that stimulates Ca2+ influx

Nature. 1993 Aug 26;364(6440):809-14. doi: 10.1038/364809a0.


Intracellular Ca2+ signals that last more than a few minutes after the onset of stimulation depend critically on influx of extracellular Ca2+. Such Ca2+ influx can be triggered in many cell types by depletion of intracellular Ca2+ stores without detectable elevations of known messengers. The mechanism by which store depletion can control plasma membrane Ca2+ permeability remains controversial. Here we present evidence for a novel soluble mediator. Calcium depletion of a lymphocyte cell line caused the messenger to be released from intracellular organelles into the cytoplasm and to a much lesser extent into the extracellular medium. The messenger caused Ca2+ influx when applied to macrophages, astrocytoma cells, and fibroblasts and was therefore named CIF (for Ca(2+)-influx factor). CIF appears to have hydroxyls (or hydroxyl and amino groups) on adjacent carbons, a phosphate, and a M(r) under 500.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Astrocytoma
  • Biological Factors / chemistry
  • Biological Factors / metabolism*
  • Calcium / metabolism*
  • Cell Membrane / metabolism
  • Cytosol / metabolism
  • Fatty Acids / pharmacology
  • Fibroblasts
  • Hexokinase / pharmacology
  • Humans
  • Macrophages
  • Organelles / metabolism
  • Phytohemagglutinins / pharmacology
  • Second Messenger Systems*
  • Serum Albumin, Bovine / pharmacology
  • T-Lymphocytes
  • Tumor Cells, Cultured


  • Biological Factors
  • Fatty Acids
  • Phytohemagglutinins
  • Serum Albumin, Bovine
  • Hexokinase
  • Calcium