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

• Published in: Journal of neuroscience research 2000-01, Vol.59 (2), p.276-282
• Main Authors: Holden, Clark P., Haughey, Norman J., Dolhun, Brian, Shepel, P. Nickolas, Nath, Avindra, Geiger, Jonathan D.
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphate - pharmacology; Astrocytes - chemistry; Astrocytes - drug effects; Astrocytes - metabolism; Bradykinin - pharmacology; Caffeine - pharmacology; Calcium - metabolism; Central Nervous System Stimulants - pharmacology; diadenosine polyphosphates; Dinucleoside Phosphates - pharmacology; Extracellular Space - metabolism; Fetus - cytology; human fetal astrocytes; Humans; Inositol 1,4,5-Trisphosphate - metabolism; Macrocyclic Compounds; Oxazoles - pharmacology; Receptors, Purinergic P2 - metabolism; Receptors, Purinergic P2X; Receptors, Purinergic P2Y1; Ryanodine - pharmacology; Ryanodine Receptor Calcium Release Channel - metabolism; Vasoconstrictor Agents - pharmacology; xestospongin
• ISSN: 0360-4012; 1097-4547
• DOI: 10.1002/(SICI)1097-4547(20000115)59:2<276::AID-JNR14>3.0.CO;2-V

Diadenosine polyphosphates (ApnAs, 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 and 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. J. Neurosci. Res. 59:276–282, 2000 © 2000 Wiley‐Liss, Inc.