Pharmacological Sensitivity of ATP Release Triggered by Photoliberation of Inositol-1,4,5-Trisphosphate and Zero Extracellular Calcium in Brain Endothelial Cells

Katleen Braet, Sandrine Aspeslagh, Wouter Vandamme, Klaus Willecke, Patricia E.M. Martin, W. Howard Evans, Luc Leybaert*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

107 Citations (Scopus)

Abstract

Recently, ATP has gained much interest as an extracellular messenger involved in the communication of calcium signals between cells. The mechanism of ATP release is, however, still a matter of debate. In the present study we investigated the possible contribution of connexin hemichannels or ion channels in the release of ATP in GP8, a rat brain endothelial cell line. Release of ATP was triggered by photoactivation of InsP3 or by reducing the extracellular calcium concentration. Both trigger protocols induced ATP release significantly above baseline. InsP3-triggered ATP release was completely blocked by α-glycyrrhetinic acid (α-GA), the connexin mimetic peptides gap 26 and 27, and the trivalent ions gadolinium and lanthanum. ATP release triggered by zero calcium was, in addition to these substances, also blocked by flufenamic acid (FFA), niflumic acid, and NPPB. Gap 27 selectively blocked zero calcium-triggered ATP release in connexin-43 transfected HeLa cells, while having no effect in wild-type and connexin-32 transfected cells. Of all the agents used, only α-GA, FFA and NPPB significantly reduced gap junctional coupling. In conclusion, InsP3 and zero calcium-triggered ATP release show major similarities but also some differences in their sensitivity to the agents applied. It is suggested that both stimuli trigger ATP release through the same mechanism, which is connexin-dependent, permeable in both directions, potently blocked by connexin mimetic peptides, and consistent with the opening of connexin hemichannels.
Original languageEnglish
Pages (from-to)205-213
Number of pages9
JournalJournal of Cellular Physiology
Volume197
Issue number2
DOIs
Publication statusPublished - Nov 2003
Externally publishedYes

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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