Nicotinic acid-adenine dinucleotide phosphate mobilizes Ca²⁺ from a thapsigargin-insensitive pool

Nicotinic acid-adenine dinucleotide phosphate (NAADP) is a novel intracellular Ca²⁺ releasing agent recently described in seaurchin eggs and egg homogenates. Ca²⁺ release by NAADP is independent of that induced by either inositol trisphosphate (InsP₃) or cyclic adenosine dinucleotide phosphate (cADPR). We now report that in sea urchin egg homogenates, NAADP releases Ca²⁺ from a Ca²⁺ pool that is distinct from those that are sensitive to InsP₃ and cADPR. This organelle has distinct Ca²⁺ uptake characteristics: it is insensitive to thapsigargin and cyclopiazoic acid, but maintenance of the pool shows some requirement for ATP. Although the different Ca²⁺ pools have different characteristics, there appears to be some degree of overlap or cross-talk between the NAADP- and cADPR/InsP₃-sensitive Ca²⁺ pools. Ca²⁺-induced Ca²⁺ release is unlikely to account for the apparent overlap between stores, since NAADP-induced Ca²⁺ release, in contrast with that stimulated by cADPR, is not potentiated by bivalent cations.