Cyclic ADP-ribose as a second messenger revisited from a new aspect of signal transduction from receptors to ADP-ribosyl cyclase.
Cyclic ADP-ribose (cADPR), an endogenous modulator of ryanodine receptor Ca(2+)-releasing channels, is found in various tissues. Cytosolic injection of cADPR induces an elevation of intracellular Ca(2+) concentrations or potentiates Ca(2+) increases. cADPR facilitates neurotransmitter or insulin release and modifies ionic currents. cADPR is synthesized by ADP-ribosyl cyclase and is metabolized by cADPR hydrolase. ADP-ribosyl cyclase activity is up-regulated by nitric oxide/cyclic GMP-dependent phosphorylation or receptor stimulation via G-proteins within membranes. These findings suggest that cADPR is a second messenger in cellular Ca(2+) signaling. However, many intriguing issues remain to be addressed before this identity is confirmed.
Higashida
H
H
Department of Biophysical Genetics, Molecular Medicine and Bioinformatics, Kanazawa University Graduate School of Medicine, 13-1 Takara-machi, 920-8640, Kanazawa, Japan. haruhiro@med.kanazawa-u.ac.jp
Hashii
M
M
Yokoyama
S
S
Hoshi
N
N
Chen
X L
XL
Egorova
A
A
Noda
M
M
Zhang
J S
JS
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000246:Adenosine Diphosphate Ribose / Q000031:analogs & derivatives* / Q000378:metabolism*; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000378:metabolism*; D001665:Binding Sites; D002478:Cells, Cultured; D036563:Cyclic ADP-Ribose; D006801:Humans; D008562:Membrane Glycoproteins; D008956:Models, Chemical; D009244:NAD+ Nucleosidase / Q000378:metabolism*; D010766:Phosphorylation; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D015398:Signal Transduction
D015703:Antigens, CD; D000943:Antigens, Differentiation; D008562:Membrane Glycoproteins; D019837:Ryanodine Receptor Calcium Release Channel; D036563:Cyclic ADP-Ribose; D000246:Adenosine Diphosphate Ribose; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1