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Second messenger function and the structure–activity relationship of cyclic adenosine diphosphoribose (cADPR)
Author(s) -
Guse Andreas H.
Publication year - 2005
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2005.04863.x
Subject(s) - cyclic adp ribose , second messenger system , ryanodine receptor , intracellular , cytosol , nad+ kinase , chemistry , biochemistry , adenosine , receptor , cd38 , biophysics , stereochemistry , microbiology and biotechnology , biology , enzyme , stem cell , cd34
Cyclic ADP‐ribose (cADPR) is a Ca 2+ mobilizing second messenger found in various cell types, tissues and organisms. Receptor‐mediated formation of cADPR may proceed via transmembrane shuttling of the substrate NAD and involvement of the ectoenzyme CD38, or via so far unidentified ADP‐ribosyl cyclases located within the cytosol or in internal membranes. cADPR activates intracellular Ca 2+ release via type 2 and 3 ryanodine receptors. The exact molecular mechanism, however, remains to be elucidated. Possibilities are the direct binding of cADPR to the ryanodine receptor or binding via a separate cADPR binding protein. In addition to Ca 2+ release, cADPR also evokes Ca 2+ entry. The underlying mechanism(s) may comprise activation of capacitative Ca 2+ entry and/or activation of the cation channel TRPM2 in conjunction with adenosine diphosphoribose. The development of novel cADPR analogues revealed new insights into the structure–activity relationship. Substitution of either the northern ribose or both the northern and southern ribose resulted in much simpler molecules, which still retained significant biological activity.