title: NAADP, cADPR and IP3 all release Ca2+ from the endoplasmic reticulum and an acidic store in the secretory granule area.
abstract: Inositol trisphosphate and cyclic ADP-ribose release Ca2+ from the endoplasmic reticulum via inositol trisphosphate and ryanodine receptors, respectively. By contrast, nicotinic acid adenine dinucleotide phosphate may activate a novel Ca2+ channel in an acid compartment. We show, in two-photon permeabilized pancreatic acinar cells, that the three messengers tested could each release Ca2+ from the endoplasmic reticulum and also from an acid store in the granular region. The nicotinic acid adenine dinucleotide phosphate action on both types of store, like that of cyclic ADP-ribose but unlike inositol trisphosphate, depended on operational ryanodine receptors, since it was blocked by ryanodine or ruthenium red. The acid Ca2+ store in the granular region did not have Golgi or lysosomal characteristics and might therefore be associated with the secretory granules. The endoplasmic reticulum is predominantly basal, but thin extensions penetrate into the granular area and cytosolic Ca2+ signals probably initiate at sites where endoplasmic reticulum elements and granules come close together.
authors.affiliation: MRC Secretory Control Research Group, The Physiological Laboratory, University of Liverpool, Crown Street, Liverpool, L69 3BX, UK. o.v.gerasimenko@liv.ac.uk
authors.forename: Julia V
authors.initials: JV
authors.lastname: Gerasimenko
authors.forename: Mark
authors.initials: M
authors.lastname: Sherwood
authors.forename: Alexei V
authors.initials: AV
authors.lastname: Tepikin
authors.forename: Ole H
authors.initials: OH
authors.lastname: Petersen
authors.forename: Oleg V
authors.initials: OV
authors.lastname: Gerasimenko
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology; D002478:Cells, Cultured; D036563:Cyclic ADP-Ribose / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D007476:Ionophores / Q000378:metabolism; D018942:Macrolides / Q000378:metabolism; D051379:Mice; D009249:NADP / Q000031:analogs & derivatives* / Q000378:metabolism; D009550:Nigericin / Q000378:metabolism; D010179:Pancreas / Q000166:cytology; D022142:Secretory Vesicles / Q000378:metabolism*; D019284:Thapsigargin / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D007476:Ionophores; D018942:Macrolides; C057620:bafilomycin A; D036563:Cyclic ADP-Ribose; D009249:NADP; C024376:NAADP; D019284:Thapsigargin; D015544:Inositol 1,4,5-Trisphosphate; D009550:Nigericin; D002118:Calcium