AJP - Cell Physiology, Vol 271, Issue 1 C43-C53, Copyright © 1996 by American Physiological Society

ARTICLES

Paracrine mediation of calcium signaling in human SK-N-MCIXC neuroepithelioma cells

R. K. Palmer, D. I. Yule, D. S. Shewach, J. A. Williams and S. K. Fisher
Neuroscience Laboratory, University of Michigan, Ann Arbor 48104-1687, USA.

Paracrine-mediated Ca2+ signaling in SK-N-MCIXC neuroepithelioma cells was evaluated by means of two experimental paradigms. In the first, single SK-N-MCIXC cells were microinjected with inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] and cytoplasmic Ca2+ was monitored by fura 2 digital-imaging microfluorometry. In response to Ins(1,4,5)P3 or CaCl2, but not inositol 1,3,4-trisphosphate, an increase in cytoplasmic Ca2+ concentration ([Ca2+]i) was observed in injected cells and also in neighboring cells. The direction of intercellular propagation of Ca2+ signals was influenced by the presence of a flow in the extracellular medium and occurred in the absence of any detectable gap-junctional communication. The P2 purinoceptor antagonist suramin, but not antagonists of other phosphoinositide-linked receptors, blocked cell-to-cell Ca2+ signaling initiated by microinjections of Ins(1,4,5)P3. In the second paradigm, conditioned medium (CM) obtained from monolayers of SK-N-MCIXC cells elicited increases in [Ca2+]i when reapplied to cells on coverslips. The Ca(2+)-mobilizing activity of CM was reversibly antagonized by suramin and abolished by pretreatment with apyrase. The presence of nucleotide di- and triphosphates in CM was confirmed by high-performance liquid chromatography. We conclude that SK-N-MCIXC cells release nucleotides that then activate specific receptors on neighboring cells. A rise in [Ca2+]i in these cells, and subsequent additional release of nucleotides, serves to further the propagation of intercellular Ca2+ signals.

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