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

• Published in: Current biology Vol. 9; no. 14; pp. 751 - 754
• Main Authors: Bak, Judit, White, Peter, Timár, György, Missiaen, Ludwig, Genazzani, Armando A., Galione, Antony
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 15.07.1999
• Subjects: 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
• ISSN: 0960-9822; 1879-0445
• 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 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.