Cyclic ADP-ribose as a potential second messenger for neuronal Ca2+ signaling.
Cyclic ADP-ribose (cADPR), a known endogenous modulator of ryanodine receptor Ca2+ releasing channels, is found in the nervous system. Injection of cADPR into neuronal cells primarily induces a transient elevation of intracellular Ca2+ concentration ([Ca2+]i), and/or secondarily potentiates [Ca2+]i increases that are the result of depolarization-induced Ca2+ influx. Acetylcholine release from cholinergic neurons is facilitated by cADPR. cADPR modifies K+ currents or elicits Ca2+-dependent inward currents. cADPR is synthesized by both membrane-bound and cytosolic forms of ADP-ribosyl cyclase in neuronal cells. cADPR hydrolase activity is weak in the membrane fraction, but high in the cytoplasm. Cytosolic ADP-ribosyl cyclase activity is upregulated by nitric oxide/cyclic GMP-dependent phosphorylation. Stimulation of muscarinic and beta-adrenergic receptors activates membrane-bound ADP-ribosyl cyclase via G proteins within membranes of neuronal tumor cells and cortical astrocytes. These findings strongly suggest that cADPR is a second messenger in Ca2+ signaling in the nervous system, although 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, Japan. haruhiro@med.kanazawa-u.ac.jp
Hashii
M
M
Yokoyama
S
S
Hoshi
N
N
Asai
K
K
Kato
T
T
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000109:Acetylcholine / Q000378:metabolism; D000246:Adenosine Diphosphate Ribose / Q000031:analogs & derivatives* / Q000378:metabolism*; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D036563:Cyclic ADP-Ribose; D006801:Humans; D008562:Membrane Glycoproteins; D009244:NAD+ Nucleosidase / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism; D015290:Second Messenger Systems / Q000502:physiology*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D008562:Membrane Glycoproteins; D036563:Cyclic ADP-Ribose; D000246:Adenosine Diphosphate Ribose; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1; D000109:Acetylcholine; D011188:Potassium