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

  title={Second messenger function and the structure–activity relationship of cyclic adenosine diphosphoribose (cADPR)},
  author={Andreas H. Guse},
  journal={The FEBS Journal},
  • A. Guse
  • Published 1 September 2005
  • Biology, Chemistry
  • The FEBS Journal
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… 

Paracrine ADP Ribosyl Cyclase-Mediated Regulation of Biological Processes

How type II CD38, Cx43 and CNTs also play a role in mediating several paracrine processes where an ADPRC+ cell supplies a neighboring CNT-and RyR-expressing cell with cADPR is discussed.

8-Bromo-cyclic inosine diphosphoribose: towards a selective cyclic ADP-ribose agonist

8-Br-N1-cIDPR appears to be the first cADPR agonist affecting Ca2+ release and secondary Ca2- entry, but without effect on TRPM2.

Synthesis and use of cell-permeant cyclic ADP-ribose.

Regulation of calcium signalling by adenine-based second messengers.

This work has shown that activation of specific plasma membrane receptors is connected to cADPR formation in many cell types and tissues, and receptor-mediated formation of NAADP and ADPR has been shown only in a few selected cellular systems.

cADPR stimulates SERCA activity in Xenopus oocytes.

Regulation of the renal microcirculation by ryanodine receptors and calcium-induced calcium release

RyR and CICR are important regulations of Ca2+ signaling and contractile tone of renal resistance arterioles in healthy kidneys and the role of this novel-signaling pathway in pathophysiological mechanisms awaits investigation.

Synthesis and Biological Evaluation of a New Structural Simplified Analogue of cADPR, a Calcium-Mobilizing Secondary Messenger Firstly Isolated from Sea Urchin Eggs

The synthesis of cpIPP, which is a new structurally-reduced analogue of cyclic ADP-ribose (cADPR), a potent Ca2+-releasing secondary messenger that was firstly isolated from sea urchin eggs extracts, revealed to be the only one provided with Ca 2+ release properties.

Second messenger analogues highlight unexpected substrate sensitivity of CD38: total synthesis of the hybrid “L-cyclic inosine 5′-diphosphate ribose”

Results highlight the key role of the “northern” ribose in the interaction of cADPR with CD38 and suggest that 8-Br-L-cIDPR potentially binds non-productively in an upside-down fashion.

cADPR Does Not Activate TRPM2

It is shown that the N-terminal MHR1/2 domain and the C-terminals NUDT9H domain are required for activation of human TRPM2 by ADPR and 2′-deoxy-ADPR (2dADPR), and that pure cADPR does not activate TR PM2 under a variety of conditions that have previously been shown to result in channel activation.

New Molecular Mechanisms on the Activation of TRPM2 Channels by Oxidative Stress and ADP-Ribose

The effects of various inhibitors such as flufenamic acid and PARP inhibitors on ADPR, NAD+ and H2O2-induced TRPM2 currents are reviewed, and inhibitor roles of antioxidants are summarized.



Regulation of calcium signaling by the second messenger cyclic adenosine diphosphoribose (cADPR).

  • A. Guse
  • Biology
    Current molecular medicine
  • 2004
The role of cADPR in a cell system studied in detail, human T-lymphocytes, and the mechanisms of c ADPR-mediated Ca2+ release and Ca2+.

Cyclic ADP ribose activation of the ryanodine receptor is mediated by calmodulin

It is reported that sea urchin egg microsomes purified by Percoll gradients lose sensitivity to cADPR, but the response can be restored by a soluble protein in the supernatant, indicating that it is calmodulin.

Autocrine and Paracrine Calcium Signaling by the CD38/NAD+/Cyclic ADP‐Ribose System

This paradox is solved by identifying some NAD+ and cADPR transmembrane transporters, whose interplay mediates a hitherto‐unrecognized subcellular and intercellular trafficking of nucleotides that enhances intracellular Ca2+ ([Ca2+]i).

Structure and enzymology of ADP-ribosyl cyclases: conserved enzymes that produce multiple calcium mobilizing metabolites.

Cyclic ADP-ribose is an important calcium mobilizing metabolite produced by the ADP-ribosyl cyclase (cyclases) family of enzymes. Three evolutionarily conserved ADP-ribosyl cyclase superfamily

Equilibrative and Concentrative Nucleoside Transporters Mediate Influx of Extracellular Cyclic ADP-Ribose into 3T3 Murine Fibroblasts*

Results suggest possible, hitherto unrecognized, correlations between ectocellular metabolism of nucleotides/nucleosides and cADPR-mediated regulation of intracellular calcium homeostasis.

Novel hydrolysis-resistant analogues of cyclic ADP-ribose: modification of the "northern" ribose and calcium release activity.

Three novel analogues modified in the "northern" ribose (ribose linked to N1 of adenine) of the Ca(2+) mobilizing second messenger cyclic adenosine diphosphoribose were synthesized and spectroscopically characterized, and the pK(a) values for the 6-amino/imino transition were determined in two cases.

Chemistry of cyclic ADP-ribose and its analogs.

The key 18-membereding construction was significantly improved by employing the phenylthiophosphate-type substrates, and the chemically and biologically stable cADPR mimic, cADP-carbocyclic-ribose (cADPcR), was synthesized.