Two modes of secretion in pancreatic acinar cells: Involvement of phosphatidylinositol 3-kinase and regulation by capacitative Ca2+ entry

Campos-Toimil, Manuel, Bagrij, Tanya, Edwardson, J. Michael and Thomas, Paul (2002) Two modes of secretion in pancreatic acinar cells: Involvement of phosphatidylinositol 3-kinase and regulation by capacitative Ca2+ entry. Current Biology, 12 (3). pp. 211-215. ISSN 0960-9822

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Abstract

In pancreatic acinar cells, muscarinic agonists stimulate both the release of Ca2+ from intracellular stores and the influx of extracellular Ca2+. The part played by Ca2+ released from intracellular stores in the regulation of secretion is well established; however, the role of Ca2+ influx in exocytosis is unclear. Recently, we observed that supramaximal concentrations of acetylcholine (≥10 μM) elicited an additional component of exocytosis despite reducing Ca2+ influx. In the present study, we found that supramaximal exocytosis was substantially inhibited (∼70%) by wortmannin (100 nM), an inhibitor of phosphatidylinositol 3-kinase. In contrast, exocytosis evoked by a lower concentration of acetylcholine (1 μM) was potentiated (∼45%) by wortmannin. Exocytosis stimulated by 1 μM acetylcholine in the absence of extracellular Ca2+ was, like supramaximal exocytosis, inhibited by wortmannin. The switch to a wortmannin-inhibitable form of exocytosis depended upon a reduction in Ca2+ entry through store-operated Ca2+ channels, as the switch in exocytotic mode could also be brought about by the selective blockade of these channels by Gd3+ (2 μM), but not by inhibition of noncapacitative Ca2+ entry by SB203580 (10 μM). We conclude that supramaximal doses of acetylcholine lead to a switch in the mode of zymogen granule exocytosis by inhibiting store-dependent Ca2+ influx.

Item Type:	Article
Faculty \ School:	Faculty of Science
Depositing User:	EPrints Services
Date Deposited:	01 Oct 2010 13:37
Last Modified:	24 Oct 2022 03:14
URI:	https://ueaeprints.uea.ac.uk/id/eprint/918
DOI:	10.1016/S0960-9822(01)00661-3

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