title: Nicotinic acid adenine dinucleotide phosphate mediates Ca2+ signals and contraction in arterial smooth muscle via a two-pool mechanism.
abstract: 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.
authors.affiliation: Department of Biomedical Sciences, School of Biology, University of St Andrews, Fife, UK.
authors.forename: François-Xavier
authors.initials: FX
authors.lastname: Boittin
authors.forename: Antony
authors.initials: A
authors.lastname: Galione
authors.forename: A Mark
authors.initials: AM
authors.lastname: Evans
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002451:Cell Compartmentation / Q000502:physiology; D002469:Cell Separation; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D053496:Inositol 1,4,5-Trisphosphate Receptors; D047028:Macrocyclic Compounds; D008297:Male; D017551:Microdialysis; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009249:NADP / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D010080:Oxazoles / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011651:Pulmonary Artery / Q000166:cytology*; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors; D012433:Ryanodine / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D015290:Second Messenger Systems / Q000187:drug effects / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
chemical_list: D015220:Calcium Channels; D004791:Enzyme Inhibitors; D053496:Inositol 1,4,5-Trisphosphate Receptors; D047028:Macrocyclic Compounds; D010080:Oxazoles; D018160:Receptors, Cytoplasmic and Nuclear; C108644:xestospongin A; D012433:Ryanodine; D009249:NADP; C024376:NAADP; D002118:Calcium