Co-ordination of Ca²⁺ signalling in mammalian cells by the new Ca²⁺-releasing messenger NAADP

Ca²⁺ signalling is one of the most important means in mammalian cells of relaying the action of hormones and neurotransmitters. The great diversity of agonist-induced Ca²⁺ signatures, visualized by optical imaging techniques, can be explained by the production of intracellular messengers triggering Ca²⁺ release from internal stores and/or by different coupling of Ca²⁺ release to Ca²⁺ entry. Several messengers, such as inositol trisphosphate and cyclic ADP-ribose, have been identified to date. More recent studies have reported the important role of a newly discovered Ca²⁺ releasing messenger, nicotinic acid adenine dinucleotide phosphate (NAADP). These studies have shown important interactions of these messengers in the generation of specific Ca²⁺ signals. NAADP acts at a very low concentration and seems to have a key role in sensitising cyclic ADP-ribose and inositol trisphosphate receptors. These points will be discussed in the present review.