Inhibition of cADPR-Hydrolase by ADP-ribose potentiates cADPR synthesis from beta-NAD+

Abstract

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 beta-NAD and degradation to ADPR. We now report that ADPR, the end-product of this enzyme, releases Ca2+ at high concentrations (above 100 microM), and at lower concentrations (10-100 microM) 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.