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

Abstract

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.

Calcium release from the endoplasmic reticulum of higher plants elicited by the NADP metabolite nicotinic acid adenine dinucleotide phosphate

“…Furthermore, the tissue possesses the metabolic machinery to synthesize NAADP from its precursors NADP and nicotinic acid. The rate of NAADP production (6.5 pmol͞mg per min) is of the same order, albeit slightly slower, as has been reported in similar conditions for sea urchin and whole brain extracts (11,29).…”

“…More recently, nicotinic acid adenine dinucleotide phosphate (NAADP), a metabolite of NADP, also has been identified as a potent mobilizer of Ca 2ϩ in sea urchin eggs, pancreatic acinar cells, and brain (9)(10)(11). Pharmacological and fractionation studies (9,11,12) demonstrate that both the release mechanism and the Ca 2ϩ stores sensitive to NAADP are distinct from those that are sensitive to InsP 3 and cADPR. NAADP-dependent Ca 2ϩ release also displays biochemical features not found in the other two ligand-gated systems.…”

“…Mammalian systems contain the enzymatic machinery to synthesize and degrade NAADP (11,20), and the presence of endogenous NAADP has been inferred in Arabidopsis thaliana with desensitization experiments (2). However, NAADP is far from being described as a ubiquitously important [Ca 2ϩ ] c modulator because NAADP-dependent Ca 2ϩ -mobilization has yet to be elucidated in systems other than marine invertebrates, pancreatic acinar cells, and brain (9)(10)(11).…”

Unique kinetics of nicotinic acid–adenine dinucleotide phosphate (NAADP) binding enhance the sensitivity of NAADP receptors for their ligand

“…1 To whom correspondence should be addressed (e-mail sandip.patel!pharmacology.oxford.ac.uk). Although the effects of NAADP have been most extensively characterized in sea urchin eggs, recent studies have extended the actions of NAADP to ascidian [14] and starfish [15] oocytes, mouse pancreatic acinar cells [16,17], rat brain microsomes [18], and plant preparations [19]. These studies strongly support a general role for NAADP-mediated Ca# + signalling.…”

Widespread Distribution of Binding Sites for the Novel Ca2+-mobilizing Messenger, Nicotinic Acid Adenine Dinucleotide Phosphate, in the Brain

“…The actions of NAADP have now been extended to mammalian (18,19) and plant (20) preparations. In acinar cells of the pancreas, NAADP is thought to underlie complex Ca 2ϩ signals in response to the brain-gut peptide, cholecystokinin, by providing a "trigger" Ca 2ϩ release that is subsequently propagated by ryanodine and IP 3 receptors (18,21).…”