Increase of intracellular Ca2+ by adenine and uracil nucleotides in human midbrain-derived neuronal progenitor cells

Patrizia Rubini, Javorina Milosevic, Johannes Engelhardt, Mahmoud Al-Khrasani, Heike Franke, Attilla Heinrich, Beata Sperlagh, Sigrid C. Schwarz, Johannes Schwarz, Wolfgang Nörenberg, Peter Illes

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Nucleotides play an important role in brain development and may exert their action via ligand-gated cationic channels or G protein-coupled receptors. Patch-clamp measurements indicated that in contrast to AMPA, ATP did not induce membrane currents in human midbrain derived neuronal progenitor cells (hmNPCs). Various nucleotide agonists concentration-dependently increased [Ca2+]i as measured by the Fura-2 method, with the rank order of potency ATP > ADP > UTP > UDP. A Ca2+-free external medium moderately decreased, whereas a depletion of the intracellular Ca2+ storage sites by cyclopiazonic acid markedly depressed the [Ca2+]i transients induced by either ATP or UTP. Further, the P2Y1 receptor antagonistic PPADS and MRS 2179, as well as the nucleotide catalyzing enzyme apyrase, allmost abolished the effects of these two nucleotides. However, the P2Y1,2,12 antagonistic suramin only slightly blocked the action of ATP, but strongly inhibited that of UTP. In agreement with this finding, UTP evoked the release of ATP from hmNPCs in a suramin-, but not PPADS-sensitive manner. Immunocytochemistry indicated the co-localization of P2Y1,2,4-immunoreactivities (IR) with nestin-IR at these cells. In conclusion, UTP may induce the release of ATP from hmNPCs via P2Y2 receptor-activation and thereby causes [Ca2+]i transients by stimulating a P2Y1-like receptor.

Original languageEnglish
Pages (from-to)485-498
Number of pages14
JournalCell Calcium
Volume45
Issue number5
DOIs
Publication statusPublished - May 2009

Keywords

  • Adenine nucleotides
  • Human neuronal progenitor cells
  • Midbrain dopaminergic neurons
  • P2X receptors
  • P2Y receptors
  • Uracil nucleotides

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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    Rubini, P., Milosevic, J., Engelhardt, J., Al-Khrasani, M., Franke, H., Heinrich, A., Sperlagh, B., Schwarz, S. C., Schwarz, J., Nörenberg, W., & Illes, P. (2009). Increase of intracellular Ca2+ by adenine and uracil nucleotides in human midbrain-derived neuronal progenitor cells. Cell Calcium, 45(5), 485-498. https://doi.org/10.1016/j.ceca.2009.03.008