Inhibition of cADPR-hydrolase by ADP-ribose potentiates cADPR synthesis from β-NAD

Cyclic adenosine 5'-diphosphate ribose (cADPR) is a potent Ca²⁺ releasing agent in a number of tissues. A particular bifunctional NAD⁺ glycohydrolase is responsible for both the cyclase and hydrolase activity necessary for its synthesis from β-NAD and degradation to ADPR. We now report that ADPR, the end-product of this enzyme, releases Ca²⁺ at high concentrations (above 100 μM), and at lower concentrations (10-100 μM) inhibits the hydrolysis of cADPR and potentiates the production of cADPR from NAD⁺. This evidence suggests that ADPR may be an important modulator of the NAD⁺ glycohydrolase responsible for the production of cADPR.