Nicotinic Acid Adenine Dinucleotide Phosphate (NAADP) and Ca2+ Mobilization

Abstract

Many physiological processes are controlled by a great diversity of Ca2 + signals that depend on Ca2 + entry into the cell and/or Ca2 + release from internal Ca2 + stores. Ca2 + mobilization from intracellular stores is gated by a family of messengers including inositol-1,4,5-trisphosphate (InsP3), cyclic ADP-ribose (cADPR), and nicotinic acid adenine dinucleotide phosphate (NAADP). There is increasing evidence for a novel intracellular Ca2 + release channel that may be targeted by NAADP and that displays properties distinctly different from the well-characterized InsP3 and ryanodine receptors. These channels appear to localize on a wider range of intracellular organelles, including the acidic Ca2 + stores. Activation of the NAADP-sensitive Ca2 + channels evokes complex changes in cytoplasmic Ca2 + levels by means of channel chatter with other intracellular Ca2 + channels. The recent demonstration of changes in intracellular NAADP levels in response to physiologically relevant extracellular stimuli highlights the significance of NAADP as an important regulator of intracellular Ca2 + signaling.