Inhibition of cADPR-Hydrolase by ADP-ribose potentiates cADPR synthesis from beta-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 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.
Genazzani
A A
AA
Department of Pharmacology, Oxford University, United Kingdom.
Bak
J
J
Galione
A
A
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000246:Adenosine Diphosphate Ribose / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D036563:Cyclic ADP-Ribose; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D007700:Kinetics; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism*; D009699:N-Glycosyl Hydrolases / Q000378:metabolism*; D009243:NAD / Q000378:metabolism* / Q000494:pharmacology; D010063:Ovum / Q000187:drug effects / Q000378:metabolism*; D012617:Sea Urchins
D015703:Antigens, CD; D000943:Antigens, Differentiation; D004791:Enzyme Inhibitors; D009243:NAD; D036563:Cyclic ADP-Ribose; D000246:Adenosine Diphosphate Ribose; D009699:N-Glycosyl Hydrolases; D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D002118:Calcium