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Published online 20 October 2003. doi:10.1083/jcb.200306134
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© The Rockefeller University Press, 0021-9525/2003/10/271 $8.00
The Journal of Cell Biology, Volume 163, Number 2, 271-282

Article

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

Julia V. Gerasimenko1, Yoshio Maruyama2, Kojiro Yano1, Nick J. Dolman1, Alexei V. Tepikin1, Ole H. Petersen1 and Oleg V. Gerasimenko1

1 Medical Research Council (MRC) Secretory Control Research Group, The Physiological Laboratory, University of Liverpool, Liverpool L69 3BX, England, UK
2 Department of Physiology, Tohoku University School of Medicine, Sendai 980-8575, Japan

Address correspondence to Ole H. Petersen, MRC Secretory Control Research Group, The Physiological Laboratory, University of Liverpool, Crown Street, Liverpool L69 3BX, England, UK. Tel.: 0-151-794-5342. Fax: 0-151-794-5323. email: o.h.petersen{at}liv.ac.uk

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.

Key Words: calcium; cyclic ADP-ribose; IP3; pancreas; acinar cells

The online version of this article includes supplemental material.

Abbreviations used in this paper: 2-APB, 2-aminoethyldiphenyl borate; AM, acetoxymethyl ester; ß-NADP, ß-nicotinamide adenine dinucleotide phosphate; cADPR, cyclic ADP-ribose; IP3, inositol 1,4,5-trisphosphate; NAADP, nicotinic acid adenine dinucleotide phosphate; NADP, nicotinamide adenine dinucleotide phosphate.


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