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PMID: 14568993 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

NAADP mobilizes Ca2+ from a thapsigargin-sensitive store in the nuclear envelope by activating ryanodine receptors.

The Journal of cell biology ·Vol. 163 ·No. 2 ·2003-10-27 ·Pages 271-82

Gerasimenko JV, Maruyama Y, Yano K, Dolman NJ, Tepikin AV, Petersen OH, Gerasimenko OV

Abstract

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.

MeSH Terms
Animals Calcium/metabolism Cyclic ADP-Ribose/pharmacology Fluorescent Dyes/metabolism Inositol 1,4,5-Trisphosphate/pharmacology Mice Mice, Inbred Strains Models, Biological NADP/analogs & derivatives,pharmacology Nuclear Envelope/drug effects,metabolism,ultrastructure Pancreas/cytology Ryanodine/metabolism Ryanodine Receptor Calcium Release Channel/metabolism Thapsigargin
Chemicals
Fluorescent Dyes Ryanodine Receptor Calcium Release Channel Cyclic ADP-Ribose Ryanodine NADP NAADP Thapsigargin Inositol 1,4,5-Trisphosphate Calcium
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Gerasimenko Julia V
MRC Secretory Control Research Group, The Physiological Laboratory, University of Liverpool, Crown Street, Liverpool L69 3BX, England, UK.
Maruyama Yoshio
Yano Kojiro
Dolman Nick J
Tepikin Alexei V
Petersen Ole H
Gerasimenko Oleg V
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
Published
2003-10-27
Epub
2003-00-20
Pages
271-82
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2173522
Subset
IM
Grants
Wellcome Trust · United Kingdom
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