Cited by 140Calcium signaling and nucleotide metabolismAdenosine and Purinergic SignalingBiochemical and Molecular Research

Second messenger function and the structure–activity relationship of cyclic adenosine diphosphoribose (cADPR)

Guse, Andreas H.·2005·The FEBS Journal

Abstract

Cyclic ADP-ribose (cADPR) is a Ca2+ 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 Ca2+ 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 Ca2+ release, cADPR also evokes Ca2+ entry. The underlying mechanism(s) may comprise activation of capacitative Ca2+ 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.

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Crossref · 10.1111/j.1742-4658.2005.04863.x

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Authors
Guse, A. H.
Affiliations
University Medical Center Hamburg-Eppendorf (DE)
Corresponding author
Guse, Andreas H.
Venue
The FEBS Journal
Publisher
Wiley
Published
2005-08-26
Volume
272
Issue
18
Pages
4590-4597
ISSN
  • 1742-464X (ISSN-L)
  • 1742-4658
OpenAlex
W1969246107
Cited by
139
References
64
Citations by year
2025: 1 · 2024: 1 · 2023: 5 · 2022: 8 · 2021: 8 · 2020: 4 · 2019: 5 · 2018: 5 · 2017: 5 · 2016: 1 · 2015: 7 · 2014: 6 · 2013: 6 · 2012: 7
FWCI
1.50
Type
journal article
Language
en
Open access
closed
Locations
  • FEBS Journal (publishedVersion)
  • PubMed (publishedVersion)
Funders
Wellcome Trust
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
Keywords
cyclic ADP-ribose, second messengers, calcium mobilization, ryanodine receptor, CD38, ADP-ribosyl cyclase, NAD+, structure-activity relationship, TRPM2, store-operated calcium entry, intracellular calcium release, cation channels
MeSH terms
Animals, Calcium, Glycoproteins, Humans, Structure-Activity Relationship, Second Messenger Systems, Molecular Chaperones, Ryanodine Receptor Calcium Release Channel, Calcium Signaling, Cyclic ADP-Ribose, Clusterin

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