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Cyclic ADP-ribose as a potential second messenger for neuronal Ca2+ signaling Higashida H; Hashii M; Yokoyama S; Hoshi N; Asai K; Kato TJ Neurochem 2001[Jan]; 76 (2): 321-31Cyclic 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.|*Antigens, CD[MESH]|ADP-ribosyl Cyclase[MESH]|ADP-ribosyl Cyclase 1[MESH]|Acetylcholine/metabolism[MESH]|Adenosine Diphosphate Ribose/*analogs & derivatives/*metabolism[MESH]|Animals[MESH]|Antigens, Differentiation/metabolism[MESH]|Calcium Signaling/*physiology[MESH]|Cyclic ADP-Ribose[MESH]|Humans[MESH]|Membrane Glycoproteins[MESH]|NAD+ Nucleosidase/metabolism[MESH]|Neurons/*metabolism[MESH]|Potassium/metabolism[MESH]|Second Messenger Systems/*physiology[MESH] |
