title: NAADP mediates ATP-induced Ca2+ signals in astrocytes.
abstract: Intracellular Ca(2+) signals provide astrocytes with a specific form of excitability that enables them to regulate synaptic transmission. In this study, we demonstrate that NAADP-AM, a membrane-permeant analogue of the new second messenger nicotinic acid-adenine dinucleotide phosphate (NAADP), mobilizes Ca(2+) in astrocytes and that the response is blocked by Ned-19, an antagonist of NAADP signalling. We also show that NAADP receptors are expressed in lysosome-related acidic vesicles. Pharmacological disruption of either NAADP or lysosomal signalling reduced Ca(2+) responses induced by ATP and endothelin-1, but not by bradykinin. Furthermore, ATP increased endogenous NAADP levels. Overall, our data provide evidence for NAADP being an intracellular messenger for agonist-mediated calcium signalling in astrocytes.
authors.affiliation: Institut de Neurociències and Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra, Catalonia, Spain.
authors.forename: Miquel
authors.initials: M
authors.lastname: Barceló-Torns
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Lewis
authors.forename: Albert
authors.initials: A
authors.lastname: Gubern
authors.forename: David
authors.initials: D
authors.lastname: Barneda
authors.forename: Duncan
authors.initials: D
authors.lastname: Bloor-Young
authors.forename: Fernado
authors.initials: F
authors.lastname: Picatoste
authors.forename: Grant C
authors.initials: GC
authors.lastname: Churchill
authors.forename: Enrique
authors.initials: E
authors.lastname: Claro
authors.forename: Roser
authors.initials: R
authors.lastname: Masgrau
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D001920:Bradykinin / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D002478:Cells, Cultured; D002614:Chelating Agents / Q000378:metabolism; D004533:Egtazic Acid / Q000378:metabolism; D019332:Endothelin-1 / Q000378:metabolism; D009249:NADP / Q000031:analogs & derivatives* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002614:Chelating Agents; D019332:Endothelin-1; D004533:Egtazic Acid; D009249:NADP; C024376:NAADP; D000255:Adenosine Triphosphate; D001920:Bradykinin; D002118:Calcium