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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 β‐adrenergic receptors activates membrane‐bound ADP‐ribosyl …