title: Modulation of NAADP (nicotinic acid-adenine dinucleotide phosphate) receptors by K+ ions: evidence for multiple NAADP receptor conformations.
abstract: NAADP (nicotinic acid-adenine dinucleotide phosphate) mediates Ca2+ release from intracellular Ca2+ stores in a wide variety of cell types. In sea urchin eggs, subthreshold concentrations of NAADP can cause full inactivation of NAADP-induced Ca2+ release, an effect that may be related to the ability of the target protein to bind its ligand in an essentially irreversible manner. In the present study, we found that K+ ions inhibit dissociation of NAADP from sea urchin egg homogenates. In low K+-containing media, an addition of excess unlabelled NAADP effectively displaced bound radioligand whereas dilution of radioligand initiated only partial dissociation. The inhibitory effects of K+ on dissociation of NAADP were concentration dependent, reversible and persisted after detergent solubilization. Lowering [K+] of the medium decreased the sensitivity of NAADP receptors for their ligand in stimulating Ca2+ release, but it did not affect inactivation of NAADP-induced Ca2+ release by subthreshold concentrations of NAADP. Our results are consistent with the observation of multiple conformations of the NAADP receptor that are readily revealed in low K+-containing media.
authors.affiliation: The Old Squash Courts, Department of Physiology, University College London, Gower Street, London WC1E 6BT, UK.
authors.forename: George D
authors.initials: GD
authors.lastname: Dickinson
authors.forename: Sandip
authors.initials: S
authors.lastname: Patel
mesh_terms: D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D008954:Models, Biological; D009249:NADP / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D010063:Ovum / Q000187:drug effects / Q000378:metabolism; D010761:Phosphorus Radioisotopes; D011188:Potassium / Q000494:pharmacology*; D011487:Protein Conformation; D011869:Radioligand Assay; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000378:metabolism*; D012617:Sea Urchins
chemical_list: D010761:Phosphorus Radioisotopes; D018160:Receptors, Cytoplasmic and Nuclear; D009249:NADP; C024376:NAADP; D011188:Potassium; D002118:Calcium