title: Cyclic ADP-ribose as a potential second messenger for neuronal Ca2+ signaling.
abstract: 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.
authors.affiliation: Department of Biophysical Genetics, Molecular Medicine and Bioinformatics, Kanazawa University Graduate School of Medicine, Japan. haruhiro@med.kanazawa-u.ac.jp
authors.forename: H
authors.initials: H
authors.lastname: Higashida
authors.forename: M
authors.initials: M
authors.lastname: Hashii
authors.forename: S
authors.initials: S
authors.lastname: Yokoyama
authors.forename: N
authors.initials: N
authors.lastname: Hoshi
authors.forename: K
authors.initials: K
authors.lastname: Asai
authors.forename: T
authors.initials: T
authors.lastname: Kato
mesh_terms: 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*
chemical_list: 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