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Regulation of Synthesis of cADPR and NAADP

Chapter

Abstract

The discovery of the Ca2+ mobilizing properties of cyclic adenosine diphosphate-ribose (cADPR), a cyclic metabolite of NAD [1], and product of enzyme activities termed ADP-ribosyl cyclases [2], has engendered a number of studies aimed at investigating the regulation of synthesis of this molecule. This is important since for cADPR to satisfy the criteria of a second messenger as originally laid down by Sutherland [3], its intracellular levels must be regulated and, in particular, by signals acting at cell surface receptors [4]. Our understanding of the regulation of cADPR synthesis, although still incomplete, has come from two types of approach. The first is the biochemical studies of regulation of ADP-ribosyl cyclase activities, and the second from the development of techniques to quantify changes in cell and tissue levels of cADPR in intact cells and tissues [4]. Endogenous levels in cells and tissues are approximately in the tens of pmol/mg protein, which coincide broadly with the concentration-response relationship range for cADPR-induced Ca2+ release. The first evidence for clues as to possible regulatory mechanisms of cADPR synthesis came from studies investigating the pathway for cGMP-induced Ca2+ mobilization in sea urchin eggs [5].

Keywords

Nitric Oxide Nitric Oxide Hypoxic Pulmonary Vasoconstriction Nicotinic Acid Adenine Dinucleotide Phosphate CD38 Knockout Mouse 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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© Springer Science+Business Media New York 2002

Authors and Affiliations

  1. 1.Department of PharmacologyOxford UniversityOxfordUK

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