Diadenosine pentaphosphate increases levels of intracellular calcium in astrocytes by a mechanism involving release from caffeine/ryanodine- and IP3-sensitive stores
Cp. Holden et al., Diadenosine pentaphosphate increases levels of intracellular calcium in astrocytes by a mechanism involving release from caffeine/ryanodine- and IP3-sensitive stores, J NEUROSC R, 59(2), 2000, pp. 276-282
(1)Diadenosine polyphosphates (Ap(n)As, n = 2 to 6 phosphate groups) activa
te P2-type cell-surface adenine nucleotide purinoreceptors, increase the in
flux of calcium into neural cells, and modulate the binding of ryanodine to
ryanodine receptor-regulated intracellular calcium release channels. In th
is study, we tested the hypothesis, using single cell fluorescence techniqu
es and cultured human fetal astrocytes, that P-1, P-5-di(adenosine-5') pent
aphosphate (Ap(5)A)-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 Ap(5)A increased [Ca2+](i) to 980 +/- 150 nM
. The effect of Ap(5)A on [Ca2+](i) was mediated in part through activation
of purinoceptors and influx of extracellular calcium because the purinocep
tor antagonist pyridoxal-phosphate-6-azophenel-2', 4'-disuphonic acid block
ed by 52%, and chelation of extracellular calcium with EGTA prevented, almo
st completely, Ap(5)A-induced increases in [Ca2+](i). Implicating calcium r
elease from IP3- and ryanodine-regulated pools of intracellular calcium wer
e findings that Ap(5)A-induced increases in [Ca2+](i) were blocked, at leas
t in part, by thapsigargin, ryanodine, caffeine, and xestospongin, and AP(5
)A increased by 2-fold the production of IP3. Release of calcium from IP3-
and ryanodine-regulated intracellular pools may be an important signaling e
vent in neural cells that are exposed to Ap(5)A. (C) 2000 Wiley-Liss, Inc.