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

Curr Biol. 1999 Jul 15;9(14):751-4. doi: 10.1016/s0960-9822(99)80335-2.


Mobilization of Ca2+ from intracellular stores is an important mechanism for generating cytoplasmic Ca2+ signals [1]. Two families of intracellular Ca(2+)-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] [4] [5] [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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / drug effects*
  • Calcium / metabolism*
  • Dose-Response Relationship, Drug
  • Hydrogen-Ion Concentration
  • In Vitro Techniques
  • Microsomes / drug effects*
  • NAD / analogs & derivatives*
  • NAD / metabolism
  • NAD / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Sea Urchins
  • Signal Transduction
  • Time Factors


  • NAD
  • nicotinic acid adenine dinucleotide
  • Calcium