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Previous studies of arterial smooth muscle have shown that inositol 1,4,5-trisphosphate (IP3) and cyclic ADP-ribose mobilize Ca2+ from the sarcoplasmic reticulum. In contrast, little is known about Ca2+ mobilization by nicotinic acid adenine dinucleotide phosphate, a pyridine nucleotide derived from beta-NADP+. We show here that intracellular dialysis of nicotinic acid adenine dinucleotide phosphate (NAADP) induces spatially restricted "bursts" of Ca2+ release that initiate a global Ca2+ wave and contraction in pulmonary artery smooth muscle cells. Depletion of sarcoplasmic reticulum Ca2+ stores with thapsigargin and inhibition of ryanodine receptors with ryanodine, respectively, block the global Ca2+ waves by NAADP. Under these conditions, however, localized Ca2+ bursts are still observed. In contrast, xestospongin C, an IP3 receptor antagonist, had no effect on Ca2+ signals by NAADP. We propose that NAADP mobilizes Ca2+ via a 2-pool mechanism, and that initial Ca2+ bursts are amplified by subsequent sarcoplasmic reticulum Ca2+ release via ryanodine receptors but not via IP3 receptors.

Original publication




Journal article


Circ Res

Publication Date





1168 - 1175


Animals, Calcium, Calcium Channels, Calcium Signaling, Cell Compartmentation, Cell Separation, Dose-Response Relationship, Drug, Enzyme Inhibitors, In Vitro Techniques, Inositol 1,4,5-Trisphosphate Receptors, Macrocyclic Compounds, Male, Microdialysis, Muscle, Smooth, Vascular, NADP, Oxazoles, Patch-Clamp Techniques, Pulmonary Artery, Rats, Rats, Wistar, Receptors, Cytoplasmic and Nuclear, Ryanodine, Sarcoplasmic Reticulum, Second Messenger Systems, Vasoconstriction