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First published online January 12, 2006
doi: 10.1242/10.1242/jcs.02721

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NAADP, cADPR and IP₃ all release Ca²⁺ from the endoplasmic reticulum and an acidic store in the secretory granule area

MRC Secretory Control Research Group, The Physiological Laboratory, University of Liverpool, Crown Street, Liverpool, L69 3BX, UK

^* Author for correspondence (e-mail: o.v.gerasimenko{at}liv.ac.uk)

Accepted 29 September 2005

Inositol trisphosphate and cyclic ADP-ribose release Ca²⁺ from the endoplasmic reticulum via inositol trisphosphate and ryanodine receptors, respectively. By contrast, nicotinic acid adenine dinucleotide phosphate may activate a novel Ca²⁺ channel in an acid compartment. We show, in two-photon permeabilized pancreatic acinar cells, that the three messengers tested could each release Ca²⁺ from the endoplasmic reticulum and also from an acid store in the granular region. The nicotinic acid adenine dinucleotide phosphate action on both types of store, like that of cyclic ADP-ribose but unlike inositol trisphosphate, depended on operational ryanodine receptors, since it was blocked by ryanodine or ruthenium red. The acid Ca²⁺ store in the granular region did not have Golgi or lysosomal characteristics and might therefore be associated with the secretory granules. The endoplasmic reticulum is predominantly basal, but thin extensions penetrate into the granular area and cytosolic Ca²⁺ signals probably initiate at sites where endoplasmic reticulum elements and granules come close together.

Key words: Ca²⁺ stores, Ryanodine, Pancreas, Two-photon, Secretory granules

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