NAADP mobilizes Ca2+ from a thapsigargin-sensitive store in the nuclear envelope by activating ryanodine receptors.
Ca2+ release from the envelope of isolated pancreatic acinar nuclei could be activated by nicotinic acid adenine dinucleotide phosphate (NAADP) as well as by inositol 1,4,5-trisphosphate (IP3) and cyclic ADP-ribose (cADPR). Each of these agents reduced the Ca2+ concentration inside the nuclear envelope, and this was associated with a transient rise in the nucleoplasmic Ca2+ concentration. NAADP released Ca2+ from the same thapsigargin-sensitive pool as IP3. The NAADP action was specific because, for example, nicotineamide adenine dinucleotide phosphate was ineffective. The Ca2+ release was unaffected by procedures interfering with acidic organelles (bafilomycin, brefeldin, and nigericin). Ryanodine blocked the Ca2+-releasing effects of NAADP, cADPR, and caffeine, but not IP3. Ruthenium red also blocked the NAADP-elicited Ca2+ release. IP3 receptor blockade did not inhibit the Ca2+ release elicited by NAADP or cADPR. The nuclear envelope contains ryanodine and IP3 receptors that can be activated separately and independently; the ryanodine receptors by either NAADP or cADPR, and the IP3 receptors by IP3.
Gerasimenko
Julia V
JV
MRC Secretory Control Research Group, The Physiological Laboratory, University of Liverpool, Crown Street, Liverpool L69 3BX, England, UK.
Maruyama
Yoshio
Y
Yano
Kojiro
K
Dolman
Nick J
NJ
Tepikin
Alexei V
AV
Petersen
Ole H
OH
Gerasimenko
Oleg V
OV
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D036563:Cyclic ADP-Ribose / Q000494:pharmacology; D005456:Fluorescent Dyes / Q000378:metabolism; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D008954:Models, Biological; D009249:NADP / Q000031:analogs & derivatives* / Q000494:pharmacology*; D009685:Nuclear Envelope / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D010179:Pancreas / Q000166:cytology; D012433:Ryanodine / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism*; D019284:Thapsigargin
D005456:Fluorescent Dyes; D019837:Ryanodine Receptor Calcium Release Channel; D036563:Cyclic ADP-Ribose; D012433:Ryanodine; D009249:NADP; C024376:NAADP; D019284:Thapsigargin; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium