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Adv Exp Med Biol. 2012;740:305-23. doi: 10.1007/978-94-007-2888-2_13.

Pyridine nucleotide metabolites and calcium release from intracellular stores.

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Department of Pharmacology, University of Oxford, UK.


Ca(2+) signals are probably the most common intracellular signaling elements, controlling an extensive range of responses in virtually all cells. Many cellular stimuli, often acting at cell surface receptors, evoke Ca(2+) signals by mobilizing Ca(2+) from intracellular stores. Inositol trisphosphate (IP₃) was the first messenger shown to link events at the plasma membrane to release of Ca(2+) from the endoplasmic reticulum (ER), through activation of IP₃-gated Ca(2+) release channels (IP₃ receptors). Subsequently, two additional Ca(2+) mobilizing messengers were discovered, cADPR and NAADP. Both are metabolites of pyridine nucleotides, and may be produced by the same class of enzymes, ADP-ribosyl cyclases, such as CD38. Whilst cADPR mobilizes Ca(2+) from the ER by activation of ryanodine receptors (RyRs), NAADP releases Ca(2+) from acidic stores by a mechanism involving the activation of two pore channels (TPCs).

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