INHIBITION OF CADPR-HYDROLASE BY ADP-RIBOSE POTENTIATES CADPR SYNTHESIS FROM BETA-NAD(+)

Cyclic adenosine 5'-diphosphate ribose (cADPR) is a potent Ca2+ releas ing agent in a number of tissues. A particular bifunctional NAD(+) gly cohydrolase 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+ a t high concentrations (above 100 mu M), and at lower concentrations (1 0-100 mu M) inhibits the hydrolysis of cADPR and potentiates the produ ction of cADPR from NAD(+). This evidence suggests that ADPR may be an important modulator of the NAD(+) glycohydrolase responsible for the production of cADPR. (C) 1996 Academic Press, Inc.