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.
MRC Secretory Control Research Group, The Physiological Laboratory, University of Liverpool, Crown Street, Liverpool L69 3BX, England, UK.
Julia V
JV
Gerasimenko
Yoshio
Y
Maruyama
Kojiro
K
Yano
Nick J
NJ
Dolman
Alexei V
AV
Tepikin
Ole H
OH
Petersen
Oleg V
OV
Gerasimenko
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