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 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.
Department of Medical Biochemistry, Semmelweis University of Medicine, PO Box 262, Budapest, 1444, Hungary.
J
J
Bak
P
P
White
G
G
Timár
L
L
Missiaen
A A
AA
Genazzani
A
A
Galione
D000818:Animals; D001921:Brain / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008861:Microsomes / Q000187:drug effects*; D009243:NAD / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012617:Sea Urchins; D015398:Signal Transduction; D013997:Time Factors
D009243:NAD; C018348:nicotinic acid adenine dinucleotide; D002118:Calcium