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Cyclic ADP‐ribose as a potential second messenger for neuronal Ca 2+ signaling
Author(s) -
Higashida Haruhiro,
Hashii Minako,
Yokoyama Shigeru,
Hoshi Naoto,
Asai Kiyofumi,
Kato Taiji
Publication year - 2001
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2001.00082.x
Subject(s) - cyclic adp ribose , second messenger system , ryanodine receptor , depolarization , microbiology and biotechnology , acetylcholine , cytosol , intracellular , chemistry , muscarinic acetylcholine receptor , biology , receptor , biochemistry , biophysics , endocrinology , cd38 , enzyme , stem cell , cd34
Cyclic ADP‐ribose (cADPR), a known endogenous modulator of ryanodine receptor Ca 2+ releasing channels, is found in the nervous system. Injection of cADPR into neuronal cells primarily induces a transient elevation of intracellular Ca 2+ concentration ([Ca 2+ ] i ), and/or secondarily potentiates [Ca 2+ ] i increases that are the result of depolarization‐induced Ca 2+ influx. Acetylcholine release from cholinergic neurons is facilitated by cADPR. cADPR modifies K + currents or elicits Ca 2+ ‐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 β‐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 Ca 2+ signaling in the nervous system, although many intriguing issues remain to be addressed before this identity is confirmed.