NAADP mobilizes Ca[SUP2 ] from a thapsigargin-sensitive store in the nuclear envelope by activating ryanodine receptors.

Gerasimenko, Julia V.; Maruyama, Yoshio; Yano, Kojiro; Dolman, Nick J.; Tepikin, Alexei V.; Petersen, Ole H.; Gerasimenko, Oleg V.

Ca[SUP2 ] 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 Ca[SUP2 ] concentration inside the nuclear envelope, and this was associated with a transient rise in the nucleoplasmic CaTM concentration. NAADP released Ca[SUP2 ] from the same thapsigargin-sensitive pool as IP3. The NAADP action was specific because, for example, nicotineamide adenine dinucleotide phosphate was ineffective. The Ca[SUP2 ] release was unaffected by procedures interfering with acidic organelles (bafilomycin, brefeldin, and nigericin). Ryanodine blocked the Ca[SUP2 ]-releasing effects of NAADP, cADPR, and caffeine, but not IP[SUB3]. Ruthenium red also blocked the NAADP-elicited Ca[SUP2 ] release. IP[SUB3] receptor blockade did not inhibit the Ca][SUP2 ] 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 Ip[SUB3] receptors by IP[SUB3].

PANCREATIC acinar cells; PANCREATIC cytology; RYANODINE; NUCLEAR membranes

Journal of Cell Biology, 2003, Vol 163, Issue 2, p271

0021-9525

Academic Journal

10.1083/jcb.200306134