Cyclic ADP-ribose (cADPR) and Nicotinic Acid Adenine Dinucleotide Phosphate (NAADP): Novel Regulators of Ca 2+-Signaling and Cell Function

Ca 2+ ions are involved in the regulation of many diverse functions in animal and plant cells, e.g. muscle contraction, secretion of neurotransmitters, hormones and enzymes, fertilization of oocytes, and lymphocyte activation and proliferation. The intracellular Ca 2+ concentration can be increased by different molecular mechanisms, such as Ca 2+ influx from the extracellular space or Ca 2+ release from intracellular Ca 2+ stores. Release from intracellular Ca 2+ stores is accomplished by the small molecular compounds D-myo-inositol 1,4,5-trisphosphate (InsP 3 ), cyclic ADP-ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate (NAADP). This review concentrates on (i) receptor-mediated formation of cADPR by ADP-ribosyl cyclases, (ii) intracellular and extracellular effects of cADPR in a variety of cell types, and (iii) cADPR in the nucleus. Though our understanding of the role of NAADP is still unclear in many aspects, important recent findings are reviewed, e.g. Ca 2+ release activity and binding studies in mammalian cell types.