Diadenosine pentaphosphate increases levels of intracellular calcium in astrocytes by a mechanism involving release from caffeine/ryanodine- and IP3-sensitive stores

Clark P. Holden, Norman J. Haughey, Brian Dolhun, P. Nickolas Shepel, Avindra Nath, Jonathan D. Geiger

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Diadenosine polyphosphates (Ap(n)As, n = 2 to 6 phosphate groups) activate P2-type cell-surface adenine nucleotide purinoreceptors, increase the influx of calcium into neural cells, and modulate the binding of ryanodine to ryanodine receptor-regulated intracellular calcium release channels. In this study, we tested the hypothesis, using single cell fluorescence techniques and cultured human fetal astrocytes, that P1, P5- di(adenosine-5') pentaphosphate (Ap5A)-induced increases in levels of intracellular calcium ([Ca2+](i)) resulted from release of calcium from intracellular pools. Basal [Ca2+](i) were 141 ± 12 nM anct Ap5A increased [Ca2+](i) to 980 ±150 nM. The effect of Ap5A on [Ca2+](i) was mediated in part through activation of purinoceptors and influx of extracellular calcium because the purinoceptor antagonist pyridoxal-phosphate-6-azophenel- 2', 4'-disuphonic acid blocked by 52%, and chelation of extracellular calcium with EGTA prevented, almost completely, Ap5A-induced increases in [Ca2+](i). Implicating calcium release from IP3- and ryanodine-regulated pools of intracellular calcium were findings that Ap5A-induced increases in [Ca2+](i) were blocked, at least in part, by thapsigargin, ryanodine, caffeine, and xestospongin, and Ap5A increased by 2-fold the production of IP3. Release of calcium from IP3- and ryanodine-regulated intracellular pools may be an important signaling event in neural cells that are exposed to Ap5A.

Original languageEnglish (US)
Pages (from-to)276-282
Number of pages7
JournalJournal of Neuroscience Research
Volume59
Issue number2
DOIs
StatePublished - Jan 15 2000
Externally publishedYes

Keywords

  • Diadenosine polyphosphates
  • Human fetal astrocytes
  • Xestospongin

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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