title: Calcium signaling by cyclic ADP-ribose, NAADP, and inositol trisphosphate are involved in distinct functions in ascidian oocytes.
abstract: ADP-ribosyl cyclase catalyzes the synthesis of two structurally and functionally different Ca2+ releasing molecules, cyclic ADP-ribose (cADPR) from beta-NAD and nicotinic acid-adenine dinucleotide phosphate (NAADP) from beta-NADP. Their Ca2+-mobilizing effects in ascidian oocytes were characterized in connection with that induced by inositol 1,4,5-trisphosphate (InsP3). Fertilization of the oocyte is accompanied by a decrease in the oocyte Ca2+ current and an increase in membrane capacitance due to the addition of membrane to the cell surface. Both of these electrical changes could be induced by perfusion, through a patch pipette, of nanomolar concentrations of cADPR or its precursor, beta-NAD, into unfertilized oocytes. The changes induced by beta-NAD showed a distinctive delay consistent with its enzymatic conversion to cADPR. The cADPR-induced changes were inhibited by preloading the oocytes with a Ca2+ chelator, indicating the effects were due to Ca2+ release induced by cADPR. Consistently, ryanodine (at high concentration) or 8-amino-cADPR, a specific antagonist of cADPR, but not heparin, inhibited the cADPR-induced changes. Both inhibitors likewise blocked the membrane insertion that normally occurred at fertilization consistent with it being mediated by a ryanodine receptor. The effects of NAADP were different from those of cADPR. Although NAADP induced a similar decrease in the Ca2+ current, no membrane insertion occurred. Moreover, pretreatment of the oocytes with NAADP inhibited the post-fertilization Ca2+ oscillation while cADPR did not. A similar Ca2+ oscillation could be artificially induced by perfusing into the oocytes a high concentration of InsP3 and NAADP could likewise inhibit such an InsP3-induced oscillation. This work shows that three independent Ca2+ signaling pathways are present in the oocytes and that each is involved in mediating distinct changes associated with fertilization. The results are consistent with a hierarchical organization of Ca2+ stores in the oocyte.
authors.affiliation: Laboratoire Canaux Ioniques et Signalisation, DSV/DBMS, 17 rue des Martyrs, F-38054 Grenoble, France.
authors.forename: M
authors.initials: M
authors.lastname: Albrieux
authors.forename: H C
authors.initials: HC
authors.lastname: Lee
authors.forename: M
authors.initials: M
authors.lastname: Villaz
mesh_terms: D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000246:Adenosine Diphosphate Ribose / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002614:Chelating Agents / Q000494:pharmacology; D036563:Cyclic ADP-Ribose / Q000031:analogs & derivatives; D004594:Electrophysiology; D005306:Fertilization / Q000502:physiology; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology*; D009243:NAD / Q000494:pharmacology; D009244:NAD+ Nucleosidase / Q000378:metabolism; D009249:NADP / Q000031:analogs & derivatives* / Q000494:pharmacology; D009865:Oocytes / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D012433:Ryanodine / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology*; D014561:Urochordata / Q000502:physiology*
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D002614:Chelating Agents; D009243:NAD; D036563:Cyclic ADP-Ribose; C082175:8-aminoadenosine cyclic 3',5'-(hydrogen phosphate) 5'-ribofuranosyl ester; D012433:Ryanodine; D000246:Adenosine Diphosphate Ribose; D009249:NADP; C024376:NAADP; D015544:Inositol 1,4,5-Trisphosphate; D036541:ADP-ribosyl Cyclase; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1; D002118:Calcium