Diadenosine pentaphosphate increases levels of intracellular calcium in astrocytes by a mechanism involving release from caffeine/ryanodine- and IP3-sensitive stores
✍ Scribed by Clark P. Holden; Norman J. Haughey; Brian Dolhun; P. Nickolas Shepel; Avindra Nath; Jonathan D. Geiger
- Publisher
- John Wiley and Sons
- Year
- 2000
- Tongue
- English
- Weight
- 128 KB
- Volume
- 59
- Category
- Article
- ISSN
- 0360-4012
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✦ Synopsis
1 Diadenosine polyphosphates (Ap n As, n ϭ 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 P 1 , P 5 -di(adenosine-5') pentaphosphate (Ap 5 A)-induced increases in levels of intracellular calcium ([Ca 2ϩ ] i ) resulted from release of calcium from intracellular pools. Basal [Ca 2ϩ ] i were 141Ϯ12 nM and Ap 5 A increased [Ca 2ϩ ] i to 980 Ϯ150 nM. The effect of Ap 5 A on [Ca 2ϩ ] i was mediated in part through activation of purinoceptors and influx of extracellular calcium because the purinoceptor antagonist pyridoxal-phosphate-6azophenel-2', 4'-disuphonic acid blocked by 52%, and chelation of extracellular calcium with EGTA prevented, almost completely, Ap 5 A-induced increases in [Ca 2ϩ ] i . Implicating calcium release from IP 3 -and ryanodine-regulated pools of intracellular calcium were findings that Ap 5 Ainduced increases in [Ca 2ϩ ] i were blocked, at least in part, by thapsigargin, ryanodine, caffeine, and xestospongin, and Ap 5 A increased by 2-fold the production of IP 3 . Release of calcium from IP 3 -and ryanodine-regulated intracellular pools may be an important signaling event in neural cells that are exposed to Ap 5 A.