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

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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.
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Keywords: Adenine Dinucleotide Phosphate; Cyclic ADP-ribose; D-myo-inositol 1,4,5-trisphosphate; Guanosine triphosphate; Nicotinic Acid; Novel Regulators; Nuclear Localization; Ryanodine receptor(s); Tumor necrosis factor

Document Type: Review Article

Publication date: May 1, 2002

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  • Current Molecular Medicine is an interdisciplinary journal focused on providing the readership with current and comprehensive reviews on fundamental molecular mechanisms of disease pathogenesis, the development of molecular-diagnosis and/or novel approaches to rational treatment. The reviews should be of significant interest to basic researchers and clinical investigators in molecular medicine. Periodically the journal will invite guest editors to devote an issue on a basic research area that shows promise to advance our understanding of the molecular mechanism(s) of a disease or has potential for clinical applications.
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