Nicotinic acid adenine dinucleotide phosphate triggers Ca²⁺ release from brain microsomes

Mobilization of Ca²⁺ from intracellular stores is an important mechanism for generating cytoplasmic Ca²⁺ signals [1]. Two families of intracellular Ca²⁺-release channels - the inositol-1,4,5-trisphosphate (IP₃) receptors and the ryanodine receptors (RyRs) - have been described in mammalian tissues [2]. Recently, nicotinic acid adenine dinucleotide phosphate (NAADP), a molecule derived from NADP⁺, has been shown to trigger Ca²⁺ release from intracellular stores in invertebrate eggs [3-6] and pancreatic acinar cells [7]. The nature of NAADP-induced Ca²⁺ release is unknown but it is clearly distinct from the IP₃- and cyclic ADP ribose (cADPR)-sensitive mechanisms in eggs (reviewed in [8,9]). Furthermore, mammalian cells can synthesize and degrade NAADP, suggesting that NAADP-induced Ca²⁺ release may be widespread and thus contribute to the complexity of Ca²⁺ signalling [10,11]. Here, we show for the first time that NAADP evokes Ca²⁺ release from rat brain microsomes by a mechanism that is distinct from those sensitive to IP₃ or cADPR, and has a remarkably similar pharmacology to the action of NAADP in sea urchin eggs [12]. Membranes prepared from the same rat brain tissues are able to support the synthesis and degradation of NAADP. We therefore suggest that NAADP-mediated Ca²⁺ signalling could play an important role in neuronal Ca²⁺ signalling.